CoChat
Sign Up
Cited by 7Immune responses and vaccinationsTuberculosis Research and EpidemiologyImmunotherapy and Immune Responses

Mycobacterium bovis BCG increase the selected determinants of monocyte/macrophage activity, which were diminished in response to gastric pathogen Helicobacter pylori

Open access
Gonciarz, Weronika, Chyb, Maciej, Chmiela, Magdalena·2023·Scientific Reports
DOI 10.1038/s41598-023-30250-6PMC PMC9944772
Open this paper in CoChat — free accountOpen PDF

Abstract

High antibiotic resistance of gastric pathogen Helicobacter pylori (Hp) and the ability to escape the host immune response prompt searching for therapeutic immunomodulators. Bacillus Calmette–Guerin (BCG) vaccine with Mycobacterium bovis (Mb) is a candidate for modulation the activity of immunocompetent cells, and onco-BCG formulation was successfully used in immunotherapy of bladder cancer. We determined the influence of onco-BCG on the phagocytic capacity of human THP-1 monocyte/macrophage cells, using the model of Escherichia coli bioparticles and Hp fluorescently labeled. Deposition of cell integrins CD11b, CD11d, CD18, membrane/soluble lipopolysaccharide (LPS) receptors, CD14 and sCD14, respectively, and the production of macrophage chemotactic protein (MCP)-1 were determined. Furthermore, a global DNA methylation, was also assessed. Human THP-1 monocytes/macrophages (TIB 202) primed or primed and restimulated with onco-BCG or Hp, were used for assessment of phagocytosis towards E. coli or Hp, surface (immunostaining) or soluble activity determinants, and global DNA methylation (ELISA). THP-1 monocytes/macrophages primed/restimulated with BCG showed increased phagocytosis capacity towards E. coli fluorescent particles, elevated expression of CD11b, CD11d, CD18, CD14, sCD14, increased MCP-1 secretion and DNA methylation. Preliminary results indicate that BCG mycobacteria may also induce the phagocytosis of H. pylori by THP-1 monocytes. Priming or priming and restimulation of monocytes/macrophages with BCG resulted in an increased activity of these cells, which was negatively modulated by Hp.

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 · 10.1038/s41598-023-30250-6

Cites

Statistics

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?

  • BCG heightened the cytotoxicity of gastric cancer cells by inducing lymphocytes to secrete IFN-g.

    “Yao et al. reported that BCG heightened the cytotoxicity of GC cells by inducing lymphocytes to secrete IFN-g.”

    From Drug repurposing for cancer therapy (2024) · cites this paper as [263]

    The Introduction (page unavailable) says BCG can induce cytokines that help the immune system kill tumor cells, but discusses this in the context of bladder cancer. It does not report heightened cytotoxicity against gastric cancer cells or identify lymphocyte-secreted IFN-γ as the mechanism; the study itself examines THP-1 monocyte/macrophage activity against H. pylori. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • BCG augments the phagocytic capacity of human THP-1 monocytes/macrophages against H. pylori by increasing expression of surface integrins CD11b, CD11d, CD18, and LPS receptors CD14 and sCD14, ultimately reducing incidence of gastric cancer.

    “In addition, BCG was found to augment the phagocytic capacity of human THP-1 monocytes/macrophages against H. pylori, by increasing the expression of the surface integrins CD11b, CD11d and CD18, as well as the membrane and soluble lipopolysaccharide receptors CD14 and sCD14, ultimately reducing the incidence of GC.263”

    From Drug repurposing for cancer therapy (2024) · cites this paper as [263]

    The Results and discussion report increased CD11b, CD11d, CD18, CD14 and sCD14 after BCG exposure, and preliminary evidence that BCG-primed THP-1 monocytes engulf H. pylori. The Conclusion says the mechanisms of H. pylori phagocytosis require further study; it does not establish that the receptor increases cause it. The paper reports no reduction in gastric-cancer incidence. Page numbers are unavailable in our copy. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

Self-check

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

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

The citation lists haven’t been fetched yet

References 57 · Cited by 7

Research works printed but not linked: 56

  1. [1]Warren JR Marshall B Unidentified curved bacilli on gastric epithelium in active chronic gastritis Lancet 1983 1 1273 1275 6134060
  2. [2]Rudnicka K Backert S Chmiela M Genetic polymorphisms in inflammatory and other regulators in gastric cancer: Risks and clinical consequences Curr. Top. Microbiol. Immunol. 2019 421 53 76 10.1007/978-3-030-15138-6_3 31123885 · DOI
  3. [3]Chmiela M Kupcinskas J Pathogenesis of Helicobacter pylori infection Helicobacter 2019 24 e12638 10.1111/hel.12638 31486234 PMC6771490 · DOI
  4. [4]Papagiannakis P The role of Helicobacter pylori infection in hematological disorders Eur. J. Intern. Med. 2013 24 685 690 10.1016/j.ejim.2013.02.011 23523153 · DOI
  5. [5]Park JS Gastric autoantigenic proteins in Helicobacter pylori infection Yonsei Med. J. 2013 54 1342 1352 10.3349/ymj.2013.54.6.1342 24142637 PMC3809852 · DOI
  6. [6]Gonciarz W Autoantibodies to a specific peptide epitope of human Hsp60 (ATVLA) with homology to Helicobacter pylori HspB in H. pylori-infected patients APMIS 2019 127 139 149 10.1111/apm.1292 30746790 · DOI
  7. [7]Gonciarz W The effect of Helicobacter pylori infection and different H. pylori components on the proliferation and apoptosis of gastric epithelial cells and fibroblasts PLoS ONE 2019 14 e0220636 10.1371/journal.pone.0220636 31390383 PMC6685636 · DOI
  8. [8]Mnich E Impact of Helicobacter pylori on the healing process of the gastric barrier World J. Gastroenterol. 2016 22 7536 7558 10.3748/wjg.v22.i33.7536 27672275 PMC5011668 · DOI
  9. [9]Li B Proton-pump inhibitor and amoxicillin-based triple therapy containing clarithromycin versus metronidazole for Helicobacter pylori: A meta-analysis Microb. Pathog. 2020 142 104075 10.1016/j.micpath.2020.104075 32074497 · DOI
  10. [10]Savoldi A Carrara E Graham DY Tacconelli CE Prevalence of antibiotic resistance in Helicobacter pylori: A systematic review and meta-analysis in World Health Organization regions Gastroenterology 2018 155 1372 1382 10.1053/j.gastro.2018.07.007 29990487 PMC6905086 · DOI
  11. [11]Cui R Correlation analysis among genotype resistance, phenotype resistance and eradication effect of Helicobacter pylori Infect. Drug Resist. 2021 14 1747 1756 10.2147/IDR.S305996 34012273 PMC8127322 · DOI
  12. [12]Bujanda L The Hp-EuReg Investigators Antibiotic resistance prevalence and trends in patients infected with Helicobacter pylori in the period 2013–2020: Results of the European Registry on H. pylori Management (Hp-EuReg) Antibiotics (Basel) 2021 10 1058 10.3390/antibiotics10091058 34572640 PMC8471667 · DOI
  13. [13]Chmiela M Czkwianianc E Wadstrom T Rudnicka W Role of Helicobacter pylori surface structures in bacterial interaction with macrophages Gut 1997 40 20 24 10.1136/gut.40.1.20 9155570 PMC1027002 · DOI
  14. [14]Ramarao N Meyer TF Helicobacter pylori resists phagocytosis by macrophages: Quantitative assessment by confocal microscopy and fluorescence-activated cell sorting Infect. Immun. 2001 69 2604 2611 10.1128/IAI.69.4.2604-2611.2001 11254625 PMC98197 · DOI
  15. [15]Allen LA Phagocytosis and persistence of Helicobacter pylori Cell Microbiol. 2007 9 817 828 10.1111/j.1462-5822.2007.00906.X 17346311 · DOI
  16. [16]Grębowska A Anti-phagocitic activity of Helicobacter pylori lipopolysaccharide (LPS)—Possible modulation of the innate immune response to these bacteria Pol. J. Microbiol. 2008 57 185 192 19004238
  17. [17]Rudnicka K Helicobacter pylori-driven modulation of NK cell expansion, intracellular cytokine expression and cytotoxic activity Innate Immun. 2015 21 127 139 10.1177/1753425913518225 24448078 · DOI
  18. [18]Paziak-Domańsk B Chmiela M Jarosińska A Rudnicka W Potential role of CagA in the inhibition of T cell reactivity in Helicobacter pylori infections Cell Immunol. 2002 202 136 139 10.1006/cimm.2000.1654 10896773 · DOI
  19. [19]Matusiak A Putative consequences of exposure to Helicobacter pylori infection in patients with coronary heart disease in terms of humoral immune response and inflammation Arch. Med. Sci. 2016 12 45 54 10.5114/aoms.2015.50772 26925118 PMC4754360 · DOI
  20. [20]Miszczyk E Antigen-specific lymphocyte proliferation as a marker of immune response in guinea pigs with sustained Helicobacter pylori infection Acta Bioch. Pol. 2014 62 295 303 24918491
  21. [22]Netea MG Trained immunity: A program of innate immune memory in health and disease Science 2016 352 aaf1098 10.1126/science.aaf1098 27102489 PMC5087274 · DOI · Paper page
  22. [23]Sohrabi Y Trained immunity as a novel approach against COVID-19 with a focus on Bacillus Calmette–Guérin vaccine: Mechanisms, challenges and perspectives Clin. Transl. Immunol. 2020 9 e1228 10.1002/cti2.1228 PMC7755499 33363733 · DOI
  23. [24]Teunissen AJP Targeting trained innate immunity with nanobiologics to treat cardiovascular disease Arterioscler. Thromb. Vasc. Biol. 2021 41 1839 1850 10.1161/ATVBAHA.120.315448 33882685 PMC8159873 · DOI
  24. [25]Rusek P Wala M Druszczyńska M Fol M Infectious agents as stimuli of trained innate immunity Int. J. Mol. Sci. 2018 19 456 10.3390/ijms19020456 29401667 PMC5855678 · DOI
  25. [26]van der Heijden CDCC Epigenetics and trained immunity Antioxid. Redox Signal. 2018 10 29 1023 1040 10.1089/ars.2017.7310 PMC6121175 28978221 · DOI
  26. [27]Masihi KN Fighting infection using immunomodulatory agents Expert Opin. Biol. Ther. 2001 1 641 653 10.1517/14712598.1.4.641 11727500 · DOI
  27. [28]Yamazaki-Nakashimada MA BCG: A vaccine with multiple faces Hum. Vaccin. Immunother. 2020 16 1841 1850 10.1080/21645515.2019.1706930 31995448 PMC7482865 · DOI
  28. [29]Freyne B Marchant A Curtis N BCG-associated heterologous immunity, a historical perspective: Intervention studies in animal models of infectious diseases Trans. R. Soc. Trop. Med. Hyg. 2015 109 52 61 10.1093/trstmh/tru197 25573109 · DOI
  29. [30]Aaby P Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J. Infect. Dis. 2011 15 204 245 252 10.1093/infdis/jir240 21673035 · DOI
  30. [31]Wardhana D The efficacy of Bacillus Calmette–Guerin vaccinations for the prevention of acute upper respiratory tract infection in the elderly Acta Med. Indones. 2011 43 185 190 21979284
  31. [32]Hana J Gua X Lia Y Wu Q Mechanisms of BCG in the treatment of bladder cancer-current understanding and the prospect Biomed. Pharmacother. 2020 129 110393 10.1016/j.biopha.2020.110393 32559616 · DOI
  32. [33]Gonciarz W Krupa A Chmiela M Proregenerative cctivity of IL-33 in gastric tissue cells undergoing Helicobacter pylori-induced apoptosis Int. J. Mol. Sci. 2020 21 1801 10.3390/ijms21051801 32151084 PMC7084496 · DOI
  33. [34]Ernst JD Macrophage receptors for Mycobacterium tuberculosis Infect. Immun. 1998 66 1277 1281 10.1128/IAI.66.4.1277-1281.1998 9529042 PMC108049 · DOI
  34. [35]Vinod V Vijayrajratnam S Vasudevan AK Biswas R The cell surface adhesins of Mycobacterium tuberculosis Microbiol. Res. 2020 232 126392 10.1016/j.micres.2019.126392 31841935 · DOI
  35. [36]Gonciarz W Chyb M Chmiela M Modulation of the Helicobacter pylori interaction with host cells through Mycobacterium bovis onko-BCG vaccine on in vitro and in vivo models Microb. Health Dis. 2022 4 e735 10.26355/mhd_20229_735 · DOI
  36. [37]Squeglia F Ruggiero A De Simone A Berisio R A structural overview of mycobacterial adhesins: Key biomarkers for diagnostics and therapeutics Protein Sci. 2017 27 369 380 10.1002/pro.3346 29139177 PMC5775178 · DOI
  37. [38]Diaz-Silvestre H The 19 kD antigen of Mycobacterium tuberculosis is a major adhesin that binds the mannose receptor of THP-1 monocytic cells and promotes phagocytosis of mycobacteria Microb. Pathog. 2005 39 97 107 10.1016/j.micpath.2005.06.002 16098710 · DOI
  38. [39]Sun H Zhi K Hu L Fan Z The activation and regulation of Beta2 integrins in phagocytes and phagocytosis Front. Immunol. 2021 12 633639 10.3389/fimmu.2021.633639 33868253 PMC8044391 · DOI
  39. [41]Yao X Leukadherin-1-mediated activation of CD11b inhibits LPS-induced pro-inflammatory response in macrophages and protects mice against endotoxic shock by blocking LPS-TLR4 interaction Front. Immunol. 2019 10 215 10.3389/fimmu.2019.00215 30809230 PMC6379471 · DOI
  40. [42]Abdelbaqi M Regulation of dextran sodium sulfate induced colitis by leukocyte beta 2 integrins Lab. Investig. 2006 86 380 390 10.1038/labinvest.3700398 16482101 · DOI
  41. [43]Ehirchiou D CD11b facilitates the development of peripheral tolerance by suppressing Th17 differentiation J. Exp. Med. 2007 204 1519 1524 10.1084/jem.20062292 17562817 PMC2118631 · DOI
  42. [44]Ganguly N Mycobacterium tuberculosis secretory proteins CFP-10, ESAT-6 and the CFP10:ESAT6 complex inhibit lipopolysaccharide induced NF-kappa B transactivation by downregulation of reactive oxygen species (ROS) production Immunol. Cell Biol. 2008 86 98 106 10.1038/sj.icb.7100117 17909563 · DOI
  43. [45]Feng X Lipopolysaccharide inhibits macrophage phagocytosis of apoptotic neutrophils by regulating the production of tumour necrosis factor α and growth arrest-specific gene 6 Immunology 2011 132 287 295 10.1111/j.1365-2567.2010.03364.x 21039473 PMC3050451 · DOI
  44. [46]Walencka M The microbiological, histological, immunological and molecular determinants of Helicobacter pylori infection in guinea pigs as a convenient animal model to study pathogenicity of these bacteria and the infection dependent immune response of the host Acta Bioch. Pol. 2015 62 697 706 10.18388/abp.2015_1110 26610308 · DOI
  45. [47]Ciesielska A Matyjek M Kwiatkowska K TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling Cell Mol. Life Sci. 2021 78 1233 1261 10.1007/s00018-020-03656-y 33057840 PMC7904555 · DOI · Paper page
  46. [48]Deng M Lipopolysaccharide clearance, bacterial clearance, and systemic inflammatory responses are regulated by cell type-specific functions of TLR4 during sepsis J. Immunol. 2013 15 190 5152 5160 10.4049/jimmunol.1300496 PMC3644895 23562812 · DOI
  47. [49]Zhang M Toll-like receptor 4 is essential to preserving cardiac function and survival in low-grade polymicrobial sepsis Anesthesiology 2014 121 1270 1280 10.1097/ALN.0000000000000337 24937074 PMC4237617 · DOI
  48. [50]Poltorak A Deffective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene Science 1998 282 2085 2088 10.1126/science.282.5396.2085 9851930 · DOI · Paper page
  49. [51]Moran AP Phenotypic variation in molecular mimicry between Helicobacter pylori lipopolysaccharides and human gastric epithelial cell surface glycoforms. Acid-induced phase variation in Lewis(x) and Lewis(y) expression by H. pylori lipopolysaccharides J. Biol. Chem. 2002 22 277 5785 5795 10.1074/jbc.M108574200 11741906 · DOI
  50. [52]Grębowska A H. pylori lipopolysaccharide activity in human peripheral blood mononuclear leukocytes cultures J. Physiol. Pharmacol. 2010 61 437 442 20814071
  51. [53]Keating ST El-Osta A Epigenetics and metabolism Circ. Res. 2015 116 715 736 10.1161/CIRCRESAHA.116.303936 25677519 · DOI
  52. [54]Yang Y PSTPIP2 connects DNA methylation to macrophage polarization in CCL4-induced mouse model of hepatic fibrosis Oncogene 2018 37 6119 6135 10.1038/s41388-018-0383-0 29993036 · DOI · Paper page
  53. [55]Ji J Methionine attenuates lipopolysaccharide-induced inflammatory responses via DNA methylation in macrophages ACS Omega 2019 4 2331 2336 10.1021/acsomega.8b0357 30775649 PMC6374979 · DOI
  54. [56]Natoli G Ostuni R Adaptation and memory in immune responses Nat. Immunol. 2019 20 783 792 10.1038/s41590-019-0399-9 31213714 · DOI
  55. [57]Bekkering S In vitro experimental model of trained innate immunity in human primary monocytes Clin. Vaccine Immunol. 2016 23 926 933 10.1128/CVI.00349-16 27733422 PMC5139603 · DOI
  56. [58]Brzeziński M Nanocarriers based on block copolymers of l-proline and lactide: The effect of core crosslinking versus its pH-sensitivity on their cellular uptake Eur. Polym. J. 2021 156 110572 10.1016/j.eurpolymj.2021.110572 · DOI

Authors
Gonciarz, W., Chyb, M., & Chmiela, M.
Affiliations
University of Łódź (PL)
Corresponding author
  • Gonciarz, Weronika
  • Chmiela, Magdalena
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2023-02-22
Volume
13
Issue
1
Pages
3107-3107
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-023-30250-6
PMC
PMC9944772
OpenAlex
W4321480365
Cited by
7
References
57
Citations by year
2026: 3 · 2024: 4
FWCI
0.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Lodz Repository (University of Łódź) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Uniwersytet Łódzki (15/GNZPA/2022 (B2111001000027.07).)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
Mycobacterium bovis BCG, Helicobacter pylori, phagocytosis, CD14, soluble CD14, CD11b, CD18, MCP-1, DNA methylation, immunomodulation, lipopolysaccharide receptor
MeSH terms
BCG Vaccine, Escherichia coli, Humans, Macrophages, Monocytes, Mycobacterium bovis, Helicobacter pylori, Lipopolysaccharide Receptors

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