CoChat
Sign Up
Cited by 72

The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.

Intestinal immune responses to commensal and pathogenic protozoa

Sardinha-Silva, Aline, Alves-Ferreira, Eliza V. C., Grigg, Michael E.·2022·Frontiers in Immunology
DOI 10.3389/fimmu.2022.963723PMC PMC9533738
Open this paper in CoChat — free account

Abstract

The physical barrier of the intestine and associated mucosal immunity maintains a delicate homeostatic balance between the host and the external environment by regulating immune responses to commensals, as well as functioning as the first line of defense against pathogenic microorganisms. Understanding the orchestration and characteristics of the intestinal mucosal immune response during commensal or pathological conditions may provide novel insights into the mechanisms underlying microbe-induced immunological tolerance, protection, and/or pathogenesis. Over the last decade, our knowledge about the interface between the host intestinal mucosa and the gut microbiome has been dominated by studies focused on bacterial communities, helminth parasites, and intestinal viruses. In contrast, specifically how commensal and pathogenic protozoa regulate intestinal immunity is less well studied. In this review, we provide an overview of mucosal immune responses induced by intestinal protozoa, with a major focus on the role of different cell types and immune mediators triggered by commensal ( Blastocystis spp. and Tritrichomonas spp.) and pathogenic ( Toxoplasma gondii , Giardia intestinalis , Cryptosporidium parvum ) protozoa. We will discuss how these various protozoa modulate innate and adaptive immune responses induced in experimental models of infection that benefit or harm the host.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fimmu.2022.963723

Cites

11 of 11 references verified0 citation errors · 0 not checkable

Statistics

Figures

Figure 1 Overview of the intestinal mucosal immunity during homeostasis, commensal protozoa colonization, and pathogenic protozoa infection. (A) The homeostasis of a healthy intestine is maintained by several biochemical and cellular components that form a physical barrier, including a mucus layer that isolates the lumen from the epithelium and underlying the mucus. There is a group of specialized epithelial cells composed of enterocytes, goblet cells, and Paneth cells that secrete antimicrobial peptides (AMPs), tuft cells that constitutively express IL-25, and intraepithelial lymphocytes (IELs) that regulate epithelial growth through the secretion of TGF-β1. Underneath the epithelium is the lamina propria (LP), and the main cells involved in homeostasis are macrophages and dendritic cells (DCs) responsible for tolerance and T-cell activation. Innate lymphoid cell 3 (ILC3) is the main source of granulocyte–macrophage colony-stimulating factor (GM-CSF), while T regulatory cells (Tregs) are key to maintaining intestinal balance and tolerance through the secretion of IL-10 and TGF-β. (B) The commensal protozoa colonization is represented by two protists, Tritrichomonas ssp. and Blastocystis spp. In the small intestine, Tritrichomonas spp. secrete succinate molecules that bind in tuft cells SUCNR1 receptors, inducing these cells to release IL-25 resulting in ILC2 activation and IL-13 secretion, leading to Th2 response and goblet cells hyperplasia. Meanwhile, in the large intestine, Tritrichomonas spp. induce Th1 and Th17 immune responses by eliciting IL-1β, IL-18, and IL-17 cytokine release. Blastocystis colonization induces goblet cell hyperplasia, which leads to neutral mucin production and stimulates Th1/Th17 immune response, with IL-17 and IL-23 cytokine signatures. (C) The intestinal mucosal immunity to pathogenic protozoa infection is represented by three parasites: Toxoplasma gondii, Giardia intestinalis, and Cryptosporidium parvum. T. gondii infection is characterized by a strong Th1 immunity, tissue damage, and immunopathology. The immune response to this protozoan is characterized by high levels of IL-33- and IL-18-producing epithelial cells, as well as IL-12 production by DCs. All these three cytokines act together to induce CD4+ T cells producing IFN-γ. The infection is also characterized by Treg collapse and a loss of Paneth cells due to the high levels of IFN-γ. G. intestinalis infection is characterized by a Th17 immunity, elicited by IL-6-producing DCs and IL-17-producing CD4+ T cells. In addition, G. intestinalis increases intestinal epithelial permeability and microbial translocation, as well as enhances IgA, AMPs, nitric oxide (NO) levels, and mucin secretion. C. parvum infection is characterized by a Th1 immune response, which is associated with secretion of AMPs and IL-18 by epithelial cells, IL-12 by DCs, and IFN-γ production by both innate lymphoid cells 1 (ILC1) and CD4+ T cells. Created with BioRender.com.
Figure 1 Overview of the intestinal mucosal immunity during homeostasis, commensal protozoa colonization, and pathogenic protozoa infection. (A) The homeostasis of a healthy intestine is maintained by several biochemical and cellular components that form a physical barrier, including a mucus layer that isolates the lumen from the epithelium and underlying the mucus. There is a group of specialized epithelial cells composed of enterocytes, goblet cells, and Paneth cells that secrete antimicrobial peptides (AMPs), tuft cells that constitutively express IL-25, and intraepithelial lymphocytes (IELs) that regulate epithelial growth through the secretion of TGF-β1. Underneath the epithelium is the lamina propria (LP), and the main cells involved in homeostasis are macrophages and dendritic cells (DCs) responsible for tolerance and T-cell activation. Innate lymphoid cell 3 (ILC3) is the main source of granulocyte–macrophage colony-stimulating factor (GM-CSF), while T regulatory cells (Tregs) are key to maintaining intestinal balance and tolerance through the secretion of IL-10 and TGF-β. (B) The commensal protozoa colonization is represented by two protists, Tritrichomonas ssp. and Blastocystis spp. In the small intestine, Tritrichomonas spp. secrete succinate molecules that bind in tuft cells SUCNR1 receptors, inducing these cells to release IL-25 resulting in ILC2 activation and IL-13 secretion, leading to Th2 response and goblet cells hyperplasia. Meanwhile, in the large intestine, Tritrichomonas spp. induce Th1 and Th17 immune responses by eliciting IL-1β, IL-18, and IL-17 cytokine release. Blastocystis colonization induces goblet cell hyperplasia, which leads to neutral mucin production and stimulates Th1/Th17 immune response, with IL-17 and IL-23 cytokine signatures. (C) The intestinal mucosal immunity to pathogenic protozoa infection is represented by three parasites: Toxoplasma gondii, Giardia intestinalis, and Cryptosporidium parvum. T. gondii infection is characterized by a strong Th1 immunity, tissue damage, and immunopathology. The immune response to this protozoan is characterized by high levels of IL-33- and IL-18-producing epithelial cells, as well as IL-12 production by DCs. All these three cytokines act together to induce CD4+ T cells producing IFN-γ. The infection is also characterized by Treg collapse and a loss of Paneth cells due to the high levels of IFN-γ. G. intestinalis infection is characterized by a Th17 immunity, elicited by IL-6-producing DCs and IL-17-producing CD4+ T cells. In addition, G. intestinalis increases intestinal epithelial permeability and microbial translocation, as well as enhances IgA, AMPs, nitric oxide (NO) levels, and mucin secretion. C. parvum infection is characterized by a Th1 immune response, which is associated with secretion of AMPs and IL-18 by epithelial cells, IL-12 by DCs, and IFN-γ production by both innate lymphoid cells 1 (ILC1) and CD4+ T cells. Created with BioRender.com.CC BY · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 11 references

Research works printed but not linked: 211

  1. McGhee, 2012, Inside the mucosal immune system, PloS Biol, 10, 10.1371/journal.pbio.1001397 · DOI
  2. Kasper, 2001, Ups and downs of mucosal cellular immunity against protozoan parasites, Infect Immun, 69, 1, 10.1128/IAI.69.1.1-8.2001 · DOI
  3. Kabat, 2014, Modulation of immune development and function by intestinal microbiota, Trends Immunol, 35, 10.1016/j.it.2014.07.010 · DOI
  4. Kayama, 2012, Regulation of intestinal homeostasis by innate and adaptive immunity, Int Immunol, 24, 10.1093/intimm/dxs094 · DOI
  5. Perez-Lopez, 2016, Mucosal immunity to pathogenic intestinal bacteria, Nat Rev Immunol, 16, 10.1038/nri.2015.17 · DOI
  6. Okumura, 2018, Maintenance of intestinal homeostasis by mucosal barriers, Inflammation Regen., 38, 5, 10.1186/s41232-018-0063-z · DOI
  7. Tokuhara, 2019, A comprehensive understanding of the gut mucosal immune system in allergic inflammation, Allergol Int, 68, 17, 10.1016/j.alit.2018.09.004 · DOI
  8. Rodriguez-Sillke, 2021, Recognition of food antigens by the mucosal and systemic immune system: Consequences for intestinal development and homeostasis, Int J Med Microbiol, 311, 151493, 10.1016/j.ijmm.2021.151493 · DOI
  9. Grondin, 2020, Mucins in intestinal mucosal defense and inflammation: Learning from clinical and experimental studies, Front Immunol, 11, 10.3389/fimmu.2020.02054 · DOI
  10. Gerbe, 2012, The intestinal epithelium tuft cells: specification and function, Cell Mol Life Sci, 69, 10.1007/s00018-012-0984-7 · DOI
  11. van der Flier, 2009, Stem cells, self-renewal, and differentiation in the intestinal epithelium, Annu Rev Physiol, 71, 10.1146/annurev.physiol.010908.163145 · DOI
  12. Cohen, 2014, Border maneuvers: deployment of mucosal immune defenses against toxoplasma gondii, Mucosal Immunol, 7, 10.1038/mi.2014.25 · DOI
  13. Clevers, 2013, Paneth cells: maestros of the small intestinal crypts, Annu Rev Physiol, 75, 289, 10.1146/annurev-physiol-030212-183744 · DOI
  14. Ting, 2019, The immune function of tuft cells at gut mucosal surfaces and beyond, J Immunol, 202, 10.4049/jimmunol.1801069 · DOI
  15. Mayassi, 2018, Human intraepithelial lymphocytes, Mucosal Immunol, 11, 10.1038/s41385-018-0016-5 · DOI · Paper page
  16. Sim, 1995, Intraepithelial lymphocytes and the immune system, Adv Immunol, 58, 297, 10.1016/S0065-2776(08)60622-7 · DOI
  17. Stagg, 2018, Intestinal dendritic cells in health and gut inflammation, Front Immunol, 9, 10.3389/fimmu.2018.02883 · DOI
  18. Sun, 2020, Dendritic cell subsets in intestinal immunity and inflammation, J Immunol, 204, 10.4049/jimmunol.1900710 · DOI
  19. Spits, 2012, Innate lymphoid cells: emerging insights in development, lineage relationships, and function, Annu Rev Immunol, 30, 10.1146/annurev-immunol-020711-075053 · DOI
  20. Mortha, 2014, Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis, Science., 343, 1249288, 10.1126/science.1249288 · DOI · Paper page
  21. Bennett, 2015, Innate-like lymphocytes in intestinal infections, Curr Opin Infect Dis, 28, 10.1097/QCO.0000000000000189 · DOI
  22. Wesemann, 2013, Microbial colonization influences early b-lineage development in the gut lamina propria, Nature., 501, 10.1038/nature12496 · DOI · Paper page
  23. Kabat, 2016, The mucosal immune system and its regulation by autophagy, Front Immunol, 7, 10.3389/fimmu.2016.00240 · DOI
  24. Mowat, 2014, Regional specialization within the intestinal immune system, Nat Rev Immunol, 14, 10.1038/nri3738 · DOI
  25. Shale, 2013, CD4(+) T-cell subsets in intestinal inflammation, Immunol Rev, 252, 10.1111/imr.12039 · DOI
  26. Harrison, 2013, Regulatory T cells and immune tolerance in the intestine, Cold Spring Harb Perspect Biol, 5, :a018341, 10.1101/cshperspect.a018341 · DOI
  27. Lukes, 2015, Are human intestinal eukaryotes beneficial or commensals, PloS Pathog, 11, 10.1371/journal.ppat.1005039 · DOI
  28. del Campo, 2020, The eukaryome: Diversity and role of microeukaryotic organisms associated with animal hosts, Funct Ecol, 34, 10.1111/1365-2435.13490 · DOI
  29. Parija, 2013, Blastocystis: Taxonomy, biology and virulence, Trop Parasitol, 3, 17, 10.4103/2229-5070.113894 · DOI
  30. Zierdt, 1967, Protozoan characteristics of blastocystis hominis, Am J Clin Pathol, 48, 495, 10.1093/ajcp/48.5.495 · DOI
  31. Silberman, 1996, Human parasite finds taxonomic home, Nature., 380, 398, 10.1038/380398a0 · DOI
  32. Alfellani, 2013, Genetic diversity of blastocystis in livestock and zoo animals, Protist., 164, 497, 10.1016/j.protis.2013.05.003 · DOI
  33. Nithyamathi, 2016, Predominance of blastocystis sp. infection among school children in peninsular Malaysia, PloS One, 11, 10.1371/journal.pone.0136709 · DOI
  34. Osman, 2016, Prevalence and risk factors for intestinal protozoan infections with cryptosporidium, giardia, blastocystis and dientamoeba among schoolchildren in Tripoli, Lebanon, PloS Negl Trop Dis, 10, 10.1371/journal.pntd.0004496 · DOI
  35. Ning, 2020, Epidemiology of blastocystis infection from 1990 to 2019 in China, Infect Dis Poverty., 9, 168, 10.1186/s40249-020-00779-z · DOI
  36. Alfellani, 2013, Variable geographic distribution of blastocystis subtypes and its potential implications, Acta Trop, 126, 10.1016/j.actatropica.2012.12.011 · DOI
  37. Khademvatan, 2018, PCR-based molecular characterization of blastocystis hominis subtypes in southwest of Iran, J Infect Public Health, 11, 10.1016/j.jiph.2017.03.009 · DOI
  38. Stensvold, 2020, Pre-empting pandora's box: Blastocystis subtypes revisited, Trends Parasitol, 36, 10.1016/j.pt.2019.12.009 · DOI
  39. Higuera, 2021, Identification of multiple blastocystis subtypes in domestic animals from Colombia using amplicon-based next generation sequencing, Front Vet Sci, 8, 10.3389/fvets.2021.732129 · DOI
  40. Maloney, 2021, Wide genetic diversity of blastocystis in white-tailed deer (Odocoileus virginianus) from Maryland, USA, Microorganisms., 9, :1343, 10.3390/microorganisms9061343 · DOI
  41. Deng, 2021, New insights into the interactions between blastocystis, the gut microbiota, and host immunity, PloS Pathog, 17, 10.1371/journal.ppat.1009253 · DOI
  42. Stenzel, 1996, Blastocystis hominis revisited, Clin Microbiol Rev, 9, 10.1128/CMR.9.4.563 · DOI
  43. Chabe, 2017, Gut Protozoa: Friends or foes of the human gut microbiota, Trends Parasitol, 33, 10.1016/j.pt.2017.08.005 · DOI
  44. Shirvani, 2020, Prevalence and molecular subtyping of blastocystis from patients with irritable bowel syndrome, inflammatory bowel disease and chronic urticaria in Iran, Acta Parasitol, 65, 10.2478/s11686-019-00131-y · DOI
  45. Pena, 2020, Determination of subtypes of blastocystis sp. in Chilean patients with and without inflammatory bowel syndrome, a preliminary report, Parasite Epidemiol Control., 8, 10.1016/j.parepi.2019.e00125 · DOI
  46. Scanlan, 2014, The microbial eukaryote blastocystis is a prevalent and diverse member of the healthy human gut microbiota, FEMS Microbiol Ecol, 90, 10.1111/1574-6941.12396 · DOI
  47. Long, 2001, Blastocystis hominis modulates immune responses and cytokine release in colonic epithelial cells, Parasitol Res, 87, 10.1007/s004360100494 · DOI
  48. Puthia, 2008, Blastocystis ratti contains cysteine proteases that mediate interleukin-8 response from human intestinal epithelial cells in an NF-kappaB-dependent manner, Eukaryot Cell, 7, 10.1128/EC.00371-07 · DOI
  49. Mirza, 2011, A metronidazole-resistant isolate of blastocystis spp. is susceptible to nitric oxide and downregulates intestinal epithelial inducible nitric oxide synthase by a novel parasite survival mechanism, Infect Immun, 79, 10.1128/IAI.05632-11 · DOI
  50. Puthia, 2005, Degradation of human secretory immunoglobulin a by blastocystis, Parasitol Res, 97, 10.1007/s00436-005-1461-0 · DOI
  51. Iguchi, 2009, Expression of interferon gamma and proinflammatory cytokines in the cecal mucosa of rats experimentally infected with blastocystis sp. strain RN94-9, Parasitol Res, 105, 10.1007/s00436-009-1373-5 · DOI
  52. Kim, 2013, Goblet cells and mucins: role in innate defense in enteric infections, Pathogens., 2, 55, 10.3390/pathogens2010055 · DOI
  53. Oukka, 2008, Th17 cells in immunity and autoimmunity, Ann Rheum Dis, 10.1136/ard.2008.098004 · DOI
  54. Stockinger, 2007, Differentiation and function of Th17 T cells, Curr Opin Immunol, 19, 10.1016/j.coi.2007.04.005 · DOI
  55. Wu, 2012, [Expressions and significance of IL-17 and IL-23 in intestinal mucosa of mice infected with blastocystis hominis], Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi., 24
  56. Guillen, 2020, Eukaryome: Emerging field with profound translational potential
  57. Howitt, 2016, Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut, Science., 351, 10.1126/science.aaf1648 · DOI
  58. von Moltke, 2016, Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit, Nature., 529, 10.1038/nature16161 · DOI · Paper page
  59. Gerbe, 2016, Intestinal tuft cells: epithelial sentinels linking luminal cues to the immune system, Mucosal Immunol, 9, 10.1038/mi.2016.68 · DOI
  60. Rajeev, 2021, Enteric tuft cells in host-parasite interactions, Pathogens., 10, :1163, 10.3390/pathogens10091163 · DOI
  61. Nadjsombati, 2018, Detection of succinate by intestinal tuft cells triggers a type 2 innate immune circuit, Immunity., 49, 33, 10.1016/j.immuni.2018.06.016 · DOI · Paper page
  62. Escalante, 2016, The common mouse protozoa tritrichomonas muris alters mucosal T cell homeostasis and colitis susceptibility, J Exp Med, 213, 10.1084/jem.20161776 · DOI
  63. Chiaranunt, 2022, NLRP1B and NLRP3 control the host response following colonization with the commensal protist tritrichomonas musculis, J Immunol, 208, 10.4049/jimmunol.2100802 · DOI
  64. Kou, 2022, A murine commensal protozoan influences host glucose homeostasis by facilitating free choline generation, Appl Environ Microbiol, 88, e0241321, 10.1128/aem.02413-21 · DOI
  65. Flegr, 2014, Toxoplasmosis–a global threat. correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries, PloS One, 9, 10.1371/journal.pone.0090203 · DOI · Paper page
  66. McLeod, 2014, Human Toxoplasma infection. Toxoplasma gondii: The model apicomplexan
  67. Snyder, 2020, From initiators to effectors: Roadmap through the intestine during encounter of toxoplasma gondii with the mucosal immune system, Front Cell Infect Microbiol, 10, 10.3389/fcimb.2020.614701 · DOI
  68. Kasper, 2004, Toxoplasma gondii and mucosal immunity, Int J Parasitol, 34, 10.1016/j.ijpara.2003.11.023 · DOI
  69. Schulthess, 2008, Mucosal immunity in toxoplasma gondii infection, Parasite., 15, 10.1051/parasite/2008153389 · DOI
  70. Oldenhove, 2009, Decrease of Foxp3+ treg cell number and acquisition of effector cell phenotype during lethal infection, Immunity., 31, 10.1016/j.immuni.2009.10.001 · DOI
  71. Sher, 1992, Regulation of immunity to parasites by T cells and T cell-derived cytokines, Annu Rev Immunol, 10, 385, 10.1146/annurev.iy.10.040192.002125 · DOI
  72. Liesenfeld, 1996, Association of CD4+ T cell-dependent, interferon-gamma-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with toxoplasma gondii, J Exp Med, 184, 597, 10.1084/jem.184.2.597 · DOI
  73. Denkers, 1998, Regulation and function of T-cell-mediated immunity during toxoplasma gondii infection, Clin Microbiol Rev, 11, 10.1128/CMR.11.4.569 · DOI
  74. Dupont, 2012, Immune response and immunopathology during toxoplasmosis, Semin Immunopathol, 34, 793, 10.1007/s00281-012-0339-3 · DOI
  75. Egan, 2012, Insights into inflammatory bowel disease using toxoplasma gondii as an infectious trigger, Immunol Cell Biol, 90, 10.1038/icb.2011.93 · DOI
  76. Gorfu, 2014, Dual role for inflammasome sensors NLRP1 and NLRP3 in murine resistance to toxoplasma gondii, mBio, 5, :e01117-13, 10.1128/mBio.01117-13 · DOI
  77. Munoz, 2015, Interleukin-22 induces interleukin-18 expression from epithelial cells during intestinal infection, Immunity., 42, 10.1016/j.immuni.2015.01.011 · DOI
  78. Speer, 1998, Ultrastructure of early stages of infections in mice fed toxoplasma gondii oocysts, Parasitology., 116, 35, 10.1017/S0031182097001959 · DOI
  79. Clark, 2021, IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii, Elife, 10, :e65614, 10.7554/eLife.65614 · DOI
  80. Heimesaat, 2006, Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with toxoplasma gondii, J Immunol, 177, 10.4049/jimmunol.177.12.8785 · DOI
  81. Craven, 2012, Inflammation drives dysbiosis and bacterial invasion in murine models of ileal crohn's disease, PloS One, 7, 10.1371/journal.pone.0041594 · DOI
  82. Molloy, 2013, Intraluminal containment of commensal outgrowth in the gut during infection-induced dysbiosis, Cell Host Microbe, 14, 10.1016/j.chom.2013.08.003 · DOI
  83. Wang, 2019, Infection-induced intestinal dysbiosis is mediated by macrophage activation and nitrate production, mBio, 10, :e00935-19, 10.1128/mBio.00935-19 · DOI
  84. Raetz, 2013, Parasite-induced TH1 cells and intestinal dysbiosis cooperate in IFN-gamma-dependent elimination of paneth cells, Nat Immunol, 14, 10.1038/ni.2508 · DOI
  85. Lopez-Yglesias, 2018, T-Bet-independent Th1 response induces intestinal immunopathology during toxoplasma gondii infection, Mucosal Immunol, 11, 10.1038/mi.2017.102 · DOI
  86. Araujo, 2021, IFN-γ mediates paneth cell death via suppression of mTOR, Elife., 10, :e60478, 10.7554/eLife.60478 · DOI
  87. Egan, 2009, CCR2-dependent intraepithelial lymphocytes mediate inflammatory gut pathology during toxoplasma gondii infection, Mucosal Immunol, 2, 10.1038/mi.2009.105 · DOI
  88. Mahmoudzadeh, 2021, The role of IL-12 in stimulating NK cells against toxoplasma gondii infection: a mini-review, Parasitol Res, 120, 10.1007/s00436-021-07204-w · DOI
  89. Sasai, 2018, Host immune responses to toxoplasma gondii, Int Immunol, 30, 10.1093/intimm/dxy004 · DOI · Paper page
  90. Wagage, 2015, The group 3 innate lymphoid cell defect in aryl hydrocarbon receptor deficient mice is associated with T cell hyperactivation during intestinal infection, PloS One, 10, 10.1371/journal.pone.0128335 · DOI
  91. Sukhumavasi, 2008, TLR adaptor MyD88 is essential for pathogen control during oral toxoplasma gondii infection but not adaptive immunity induced by a vaccine strain of the parasite, J Immunol, 181, 10.4049/jimmunol.181.5.3464 · DOI
  92. Gregg, 2013, Replication and distribution of toxoplasma gondii in the small intestine after oral infection with tissue cysts, Infect Immun, 81, 10.1128/IAI.01126-12 · DOI
  93. Coombes, 2013, Motile invaded neutrophils in the small intestine of toxoplasma gondii-infected mice reveal a potential mechanism for parasite spread, Proc Natl Acad Sci U S A., 110, 10.1073/pnas.1220272110 · DOI
  94. Sardinha-Silva, 2019, The lectin-specific activity of toxoplasma gondii microneme proteins 1 and 4 binds toll-like receptor 2 and 4 n-glycans to regulate innate immune priming, PloS Pathog, 15, 10.1371/journal.ppat.1007871 · DOI
  95. Yarovinsky, 2005, TLR11 activation of dendritic cells by a protozoan profilin-like protein, Science., 308, 10.1126/science.1109893 · DOI
  96. Kucera, 2010, Structure-based analysis of toxoplasma gondii profilin: a parasite-specific motif is required for recognition by toll-like receptor 11, J Mol Biol, 403, 10.1016/j.jmb.2010.09.022 · DOI
  97. Koblansky, 2013, Recognition of profilin by toll-like receptor 12 is critical for host resistance to toxoplasma gondii, Immunity., 38, 10.1016/j.immuni.2012.09.016 · DOI
  98. Raetz, 2013, Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to toxoplasma gondii profilin, J Immunol, 191, 10.4049/jimmunol.1301301 · DOI
  99. Benson, 2009, Gut commensal bacteria direct a protective immune response against toxoplasma gondii, Cell Host Microbe, 6, 10.1016/j.chom.2009.06.005 · DOI
  100. Koshy, 2012, Toxoplasma co-opts host cells it does not invade, PloS Pathog, 8, 10.1371/journal.ppat.1002825 · DOI
  101. Chen, 2020, The toxoplasma gondii virulence factor ROP16 acts in cis and trans, and suppresses T cell responses, J Exp Med, 217, :e20181757, 10.1084/jem.20181757 · DOI
  102. Cohen, 2015, Impact of toxoplasma gondii on dendritic cell subset function in the intestinal mucosa, J Immunol, 195, 10.4049/jimmunol.1501137 · DOI
  103. Jensen, 2011, Toxoplasma polymorphic effectors determine macrophage polarization and intestinal inflammation, Cell Host Microbe, 9, 10.1016/j.chom.2011.04.015 · DOI
  104. Jensen, 2013, Toxoplasma gondii rhoptry 16 kinase promotes host resistance to oral infection and intestinal inflammation only in the context of the dense granule protein GRA15, Infect Immun, 81, 10.1128/IAI.01185-12 · DOI
  105. Kim, 2005, p38 MAPK autophosphorylation drives macrophage IL-12 production during intracellular infection, J Immunol, 174, 10.4049/jimmunol.174.7.4178 · DOI
  106. Braun, 2013, A toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation, J Exp Med, 210, 10.1084/jem.20130103 · DOI
  107. Mercer, 2020, Toxoplasma gondii dense granule protein GRA24 drives MyD88-independent p38 MAPK activation, IL-12 production and induction of protective immunity, PloS Pathog, 16, 10.1371/journal.ppat.1008572 · DOI
  108. Mukhopadhyay, 2020, Toxoplasma GRA15 and GRA24 are important activators of the host innate immune response in the absence of TLR11, PloS Pathog, 16, 10.1371/journal.ppat.1008586 · DOI
  109. Dunay, 2008, Gr1(+) inflammatory monocytes are required for mucosal resistance to the pathogen toxoplasma gondii, Immunity., 29, 10.1016/j.immuni.2008.05.019 · DOI
  110. Cohen, 2013, CXCR3-dependent CD4(+) T cells are required to activate inflammatory monocytes for defense against intestinal infection, PloS Pathog, 9, 10.1371/journal.ppat.1003706 · DOI
  111. Khan, 1997, A dichotomous role for nitric oxide during acute toxoplasma gondii infection in mice, Proc Natl Acad Sci U S A., 94, 10.1073/pnas.94.25.13955 · DOI
  112. Hunn, 2011, The immunity-related GTPases in mammals: a fast-evolving cell-autonomous resistance system against intracellular pathogens, Mamm Genome, 22, 43, 10.1007/s00335-010-9293-3 · DOI
  113. Burger, 2018, Loss of paneth cell autophagy causes acute susceptibility to toxoplasma gondii-mediated inflammation, Cell Host Microbe, 23, 177, 10.1016/j.chom.2018.01.001 · DOI
  114. Suzuki, 2000, IL-10 is required for prevention of necrosis in the small intestine and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice following peroral infection with toxoplasma gondii, J Immunol, 164, 10.4049/jimmunol.164.10.5375 · DOI
  115. Rachinel, 2004, The induction of acute ileitis by a single microbial antigen of toxoplasma gondii, J Immunol, 173, 10.4049/jimmunol.173.4.2725 · DOI
  116. Cortez, 2014, CRTAM controls residency of gut CD4+CD8+ T cells in the steady state and maintenance of gut CD4+ Th17 during parasitic infection, J Exp Med, 211, 10.1084/jem.20130904 · DOI
  117. Cervantes-Barragan, 2019, CRTAM protects against intestinal dysbiosis during pathogenic parasitic infection by enabling Th17 maturation, Front Immunol, 10, 10.3389/fimmu.2019.01423 · DOI
  118. Savioli, 2006, Giardia and cryptosporidium join the 'Neglected diseases initiative', Trends Parasitol, 22, 10.1016/j.pt.2006.02.015 · DOI
  119. Solaymani-Mohammadi, 2010, Giardia duodenalis: the double-edged sword of immune responses in giardiasis, Exp Parasitol, 126, 10.1016/j.exppara.2010.06.014 · DOI
  120. Yoder, 2012, Giardiasis surveillance–united states, 2009-2010, MMWR Surveill Summ., 61, 13
  121. Garzon, 2017, Association of enteric parasitic infections with intestinal inflammation and permeability in asymptomatic infants of sao tome island, Pathog Glob Health, 111, 10.1080/20477724.2017.1299831 · DOI
  122. Kraft, 2017, Giardia's epithelial cell interaction In vitro: Mimicking asymptomatic infection, Front Cell Infect Microbiol, 7, 10.3389/fcimb.2017.00421 · DOI
  123. Solaymani-Mohammadi, 2022, Mucosal defense against giardia at the intestinal epithelial cell interface, Front Immunol, 13, 10.3389/fimmu.2022.817468 · DOI · Paper page
  124. Mahmud, 1995, Risk factors for development of first symptomatic giardia infection among infants of a birth cohort in rural Egypt, Am J Trop Med Hyg, 53, 10.4269/ajtmh.1995.53.84 · DOI
  125. Al-Mekhlafi, 2013, Burden of giardia duodenalis infection and its adverse effects on growth of schoolchildren in rural Malaysia, PloS Negl Trop Dis, 7, 10.1371/journal.pntd.0002516 · DOI
  126. Rogawski, 2017, Determinants and impact of giardia infection in the first 2 years of life in the MAL-ED birth cohort, J Pediatr Infect Dis Soc, 6, 10.1093/jpids/piw082 · DOI
  127. Rogawski, 2018, Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study, Lancet Glob Health, 6, 10.1016/S2214-109X(18)30351-6 · DOI · Paper page
  128. Adam, 2001, Biology of giardia lamblia, Clin Microbiol Rev, 14, 10.1128/CMR.14.3.447-475.2001 · DOI
  129. Saghaug, 2016, Human memory CD4+ T cell immune responses against giardia lamblia, Clin Vaccine Immunol, 23, 10.1128/CVI.00419-15 · DOI
  130. Singer, 2019, Recent insights into innate and adaptive immune responses to giardia, Adv Parasitol, 106, 171, 10.1016/bs.apar.2019.07.004 · DOI · Paper page
  131. Muller, 2005, Recent insights into the mucosal reactions associated with giardia lamblia infections, Int J Parasitol, 35, 10.1016/j.ijpara.2005.07.008 · DOI
  132. Troeger, 2007, Effect of chronic giardia lamblia infection on epithelial transport and barrier function in human duodenum, Gut., 56, 10.1136/gut.2006.100198 · DOI · Paper page
  133. Reynoso-Robles, 2015, The invasive potential of giardia intestinalis in an in vivo model, Sci Rep, 5, 15168, 10.1038/srep15168 · DOI
  134. Eckmann, 2000, Nitric oxide production by human intestinal epithelial cells and competition for arginine as potential determinants of host defense against the lumen-dwelling pathogen giardia lamblia, J Immunol, 164, 10.4049/jimmunol.164.3.1478 · DOI
  135. Stadelmann, 2012, Arginine consumption by the intestinal parasite giardia intestinalis reduces proliferation of intestinal epithelial cells, PloS One, 7, 10.1371/journal.pone.0045325 · DOI
  136. Tako, 2013, Transcriptomic analysis of the host response to giardia duodenalis infection reveals redundant mechanisms for parasite control, mBio., 4, 10.1128/mBio.00660-13 · DOI
  137. Paerewijck, 2017, Interleukin-17 receptor a (IL-17RA) as a central regulator of the protective immune response against giardia, Sci Rep, 7, 8520, 10.1038/s41598-017-08590-x · DOI
  138. Manko, 2017, Giardia co-infection promotes the secretion of antimicrobial peptides beta-defensin 2 and trefoil factor 3 and attenuates attaching and effacing bacteria-induced intestinal disease, PloS One, 12, 10.1371/journal.pone.0178647 · DOI
  139. Manko-Prykhoda, 2020, Giardia spp. promote the production of antimicrobial peptides and attenuate disease severity induced by attaching and effacing enteropathogens via the induction of the NLRP3 inflammasome, Int J Parasitol, 50, 10.1016/j.ijpara.2019.12.011 · DOI
  140. Scott, 2002, Intestinal infection with giardia spp. reduces epithelial barrier function in a myosin light chain kinase-dependent fashion, Gastroenterology., 123, 10.1053/gast.2002.36002 · DOI
  141. Zhou, 2007, Tumour necrosis factor alpha contributes to protection against giardia lamblia infection in mice, Parasite Immunol, 29, 10.1111/j.1365-3024.2007.00953.x · DOI
  142. Chen, 2013, Persistent gut barrier damage and commensal bacterial influx following eradication of giardia infection in mice, Gut Pathog, 5, 26, 10.1186/1757-4749-5-26 · DOI
  143. Bienz, 2003, Interleukin-6-deficient mice are highly susceptible to giardia lamblia infection but exhibit normal intestinal immunoglobulin a responses against the parasite, Infect Immun, 71, 10.1128/IAI.71.3.1569-1573.2003 · DOI
  144. Zhou, 2003, Role of interleukin-6 in the control of acute and chronic giardia lamblia infections in mice, Infect Immun, 71, 10.1128/IAI.71.3.1566-1568.2003 · DOI
  145. Kamda, 2012, Giardia duodenalis: dendritic cell defects in IL-6 deficient mice contribute to susceptibility to intestinal infection, Exp Parasitol, 130, 10.1016/j.exppara.2012.01.003 · DOI
  146. Keselman, 2016, The microbiota contributes to CD8+ T cell activation and nutrient malabsorption following intestinal infection with giardia duodenalis, Infect Immun, 84, 10.1128/IAI.00348-16 · DOI
  147. Li, 2017, TLR2(-/-) mice display decreased severity of giardiasis via enhanced proinflammatory cytokines production dependent on AKT signal pathway, Front Immunol, 8, 10.3389/fimmu.2017.01186 · DOI
  148. Li, 2004, Mast cell-dependent control of giardia lamblia infections in mice, Infect Immun, 72, 10.1128/IAI.72.11.6642-6649.2004 · DOI
  149. Li, 2007, Mast cell-mediated changes in smooth muscle contractility during mouse giardiasis, Infect Immun, 75, 10.1128/IAI.00596-07 · DOI
  150. Li, 2016, Complement activation by giardia duodenalis parasites through the lectin pathway contributes to mast cell responses and parasite control, Infect Immun, 84, 10.1128/IAI.00074-16 · DOI
  151. Singer, 2000, T-Cell-dependent control of acute giardia lamblia infections in mice, Infect Immun, 68, 10.1128/IAI.68.1.170-175.2000 · DOI
  152. Andersen, 2006, Adaptive immunity-dependent intestinal hypermotility contributes to host defense against giardia spp, Infect Immun, 74, 10.1128/IAI.74.4.2473-2476.2006 · DOI
  153. Li, 2006, Neuronal nitric oxide synthase is necessary for elimination of giardia lamblia infections in mice, J Immunol, 176, 10.4049/jimmunol.176.1.516 · DOI
  154. Scott, 2004, Role of CD8+ and CD4+ T lymphocytes in jejunal mucosal injury during murine giardiasis, Infect Immun, 72, 10.1128/IAI.72.6.3536-3542.2004 · DOI
  155. Bouzid, 2013, A new heterogeneous family of telomerically encoded cryptosporidium proteins, Evol Appl, 6, 10.1111/j.1752-4571.2012.00277.x · DOI
  156. Huang, 2006, An updated review on cryptosporidium and giardia, Gastroenterol Clin North Am, 35, 291, 10.1016/j.gtc.2006.03.006 · DOI
  157. 2017, Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the global burden of disease study 2015, Lancet Infect Dis, 17, 10.1016/S1473-3099(17)30276-1 · DOI
  158. Crawford, 2021, The mucosal innate immune response to cryptosporidium parvum, a global one health issue, Front Cell Infect Microbiol, 11, 10.3389/fcimb.2021.689401 · DOI
  159. McDonald, 2013, Innate immune responses against cryptosporidium parvum infection, Parasite Immunol, 35, 55, 10.1111/pim.12020 · DOI
  160. Laurent, 2017, Innate immune responses play a key role in controlling infection of the intestinal epithelium by cryptosporidium, Int J Parasitol, 47, 10.1016/j.ijpara.2017.08.001 · DOI
  161. Lantier, 2013, Intestinal CD103+ dendritic cells are key players in the innate immune control of cryptosporidium parvum infection in neonatal mice, PloS Pathog, 9, 10.1371/journal.ppat.1003801 · DOI
  162. Lacroix-Lamande, 2002, Role of gamma interferon in chemokine expression in the ileum of mice and in a murine intestinal epithelial cell line after cryptosporidium parvum infection, Infect Immun, 70, 10.1128/IAI.70.4.2090-2099.2002 · DOI
  163. Pantenburg, 2008, Intestinal immune response to human cryptosporidium sp, infection. Infect Immun, 76, 10.1128/IAI.00960-07 · DOI
  164. Chen, 2001, Cryptosporidium parvum activates nuclear factor kappaB in biliary epithelia preventing epithelial cell apoptosis, Gastroenterology., 120, 10.1053/gast.2001.24850 · DOI
  165. Chen, 2005, Multiple TLRs are expressed in human cholangiocytes and mediate host epithelial defense responses to cryptosporidium parvum via activation of NF-kappaB, J Immunol, 175, 10.4049/jimmunol.175.11.7447 · DOI
  166. Choudhry, 2012, A protective role for interleukin 18 in interferon gamma-mediated innate immunity to cryptosporidium parvum that is independent of natural killer cells, J Infect Dis, 206, 10.1093/infdis/jis300 · DOI
  167. Korbel, 2011, CD4+ T cells are not essential for control of early acute cryptosporidium parvum infection in neonatal mice, Infect Immun, 79, 10.1128/IAI.00922-10 · DOI
  168. Urban, 1996, IL-12 protects immunocompetent and immunodeficient neonatal mice against infection with cryptosporidium parvum, J Immunol, 156, 10.4049/jimmunol.156.1.263 · DOI
  169. Mead, 1998, Susceptibility differences to cryptosporidium parvum infection in two strains of gamma interferon knockout mice, J Parasitol, 84, 10.2307/3284643 · DOI
  170. Ehigiator, 2007, Cryptosporidium parvum: the contribution of Th1-inducing pathways to the resolution of infection in mice, Exp Parasitol, 115, 10.1016/j.exppara.2006.07.001 · DOI
  171. Tessema, 2009, Dynamics of gut mucosal and systemic Th1/Th2 cytokine responses in interferon-gamma and interleukin-12p40 knock out mice during primary and challenge cryptosporidium parvum infection, Immunobiology., 214, 10.1016/j.imbio.2008.11.015 · DOI
  172. Sateriale, 2021, The intestinal parasite Cryptosporidium is controlled by an enterocyte intrinsic inflammasome that depends on NLRP6, Proc Natl Acad Sci USA, 118, :e2007807118, 10.1073/pnas.2007807118 · DOI
  173. Gullicksrud, 2022, Enterocyte-innate lymphoid cell crosstalk drives early IFN-gamma-mediated control of cryptosporidium, Mucosal Immunol, 15, 10.1038/s41385-021-00468-6 · DOI
  174. Ungar, 1991, Cryptosporidium infection in an adult mouse model. independent roles for IFN-gamma and CD4+ T lymphocytes in protective immunity, J Immunol, 147, 10.4049/jimmunol.147.3.1014 · DOI
  175. McDonald, 1994, Mechanisms of innate and acquired resistance to cryptosporidium parvum infection in SCID mice, Parasite Immunol, 16, 10.1111/j.1365-3024.1994.tb00354.x · DOI
  176. Hayward, 2000, Interferon-gamma is required for innate immunity to cryptosporidium parvum in mice, J Infect Dis, 182, 10.1086/315802 · DOI
  177. Robinson, 2001, Expression of IL-15 and IL-4 in IFN-gamma-independent control of experimental human cryptosporidium parvum infection, Cytokine., 15, 39, 10.1006/cyto.2001.0888 · DOI
  178. Barakat, 2009, Roles for NK cells and an NK cell-independent source of intestinal gamma interferon for innate immunity to cryptosporidium parvum infection, Infect Immun, 77, 10.1128/IAI.00377-09 · DOI
  179. McDonald, 2004, Protection against the early acute phase of cryptosporidium parvum infection conferred by interleukin-4-induced expression of T helper 1 cytokines, J Infect Dis, 190, 10.1086/422761 · DOI
  180. Enriquez, 1993, Role of CD4+ TH1- and TH2-cell-secreted cytokines in cryptosporidiosis, Folia Parasitol (Praha)., 40
  181. Aguirre, 1994, Susceptibility of major histocompatibility complex (MHC) class I- and MHC class II-deficient mice to cryptosporidium parvum infection, Infect Immun, 62, 10.1128/iai.62.2.697-699.1994 · DOI
  182. Chen, 2003, Cryptosporidium parvum infection in gene-targeted b cell-deficient mice, J Parasitol, 89, 10.1645/0022-3395(2003)089[0391:CPIIGB]2.0.CO;2 · DOI
  183. Frost, 2005, How clean must our drinking water be: the importance of protective immunity, J Infect Dis, 191, 10.1086/427561 · DOI
  184. Frost, 2005, Protective immunity associated with a strong serological response to a cryptosporidium-specific antigen group, in HIV-infected individuals, J Infect Dis, 192, 10.1086/431681 · DOI
  185. Dumaine, 2021, The enteric pathogen cryptosporidium parvum exports proteins into the cytosol of the infected host cell, Elife, 10, :e70451, 10.7554/eLife.70451 · DOI
  186. Wei, 2020, Commensal bacteria impact a protozoan's integration into the murine gut microbiota in a dietary nutrient-dependent manner, Appl Environ Microbiol, 86, :e00303-20, 10.1128/AEM.00303-20 · DOI
  187. Audebert, 2016, Colonization with the enteric protozoa blastocystis is associated with increased diversity of human gut bacterial microbiota, Sci Rep, 6, 25255, 10.1038/srep25255 · DOI
  188. Hatter, 2018, Toxoplasma gondii infection triggers chronic cachexia and sustained commensal dysbiosis in mice, PloS One, 13, 10.1371/journal.pone.0204895 · DOI
  189. Iebba, 2016, Gut microbiota related to giardia duodenalis, entamoeba spp. and blastocystis hominis infections in humans from cote d'Ivoire, J Infect Dev Ctries., 10, 10.3855/jidc.8179 · DOI
  190. Barash, 2017, Giardia alters commensal microbial diversity throughout the murine gut, Infect Immun, 85, :e00948, 10.1128/IAI.00948-16 · DOI
  191. Beatty, 2017, Giardia duodenalis induces pathogenic dysbiosis of human intestinal microbiota biofilms, Int J Parasitol, 47, 10.1016/j.ijpara.2016.11.010 · DOI · Paper page
  192. McKenney, 2017, Down for the count: Cryptosporidium infection depletes the gut microbiome in coquerel's sifakas, Microb Ecol Health Dis, 28, 1335165, 10.1080/16512235.2017.1335165 · DOI
  193. Mammeri, 2019, Cryptosporidium parvum-infected neonatal mice show gut microbiota remodelling using high-throughput sequencing analysis: Preliminary results, Acta Parasitol, 64, 10.2478/s11686-019-00044-w · DOI
  194. Hand, 2012, Acute gastrointestinal infection induces long-lived microbiota-specific T cell responses, Science., 337, 10.1126/science.1220961 · DOI
  195. Melgar, 2005, Acute colitis induced by dextran sulfate sodium progresses to chronicity in C57BL/6 but not in BALB/c mice: correlation between symptoms and inflammation, Am J Physiol Gastrointest Liver Physiol, 288, 10.1152/ajpgi.00467.2004 · DOI
  196. Huang, 2002, The quantity of nitric oxide released by macrophages regulates chlamydia-induced disease, Proc Natl Acad Sci U S A., 99, 10.1073/pnas.062578399 · DOI
  197. Mills, 2000, M-1/M-2 macrophages and the Th1/Th2 paradigm, J Immunol, 164, 10.4049/jimmunol.164.12.6166 · DOI · Paper page
  198. Falkow, 2006, Is persistent bacterial infection good for your health, Cell, 124, 699, 10.1016/j.cell.2006.02.004 · DOI
  199. Smith, 2013, The microbial metabolites, short-chain fatty acids, regulate colonic treg cell homeostasis, Science., 341, 10.1126/science.1241165 · DOI · Paper page
  200. Kamada, 2013, Role of the gut microbiota in the development and function of lymphoid cells, J Immunol, 190, 10.4049/jimmunol.1203100 · DOI

200 of 211 shown

Cited by

Sorted by citations

See all 72

Metadata

Authors
Sardinha-Silva, A., Alves-Ferreira, E. V. C., & Grigg, M. E.
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2022-09-16
Volume
13
ISSN
1664-3224
DOI
10.3389/fimmu.2022.963723
PMC
PMC9533738
Cited by
72
References
11
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
Division of Intramural Research, National Institute of Allergy and Infectious Diseases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Intestinal immune responses to commensal and pathogenic protozoa. https://app.cochat.ai/papers/10.3389/fimmu.2022.963723
The paper
Sardinha-Silva, A., Alves-Ferreira, E. V. C., & Grigg, M. E. (2022). Intestinal immune responses to commensal and pathogenic protozoa. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2022.963723