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Control of adaptive immunity by the innate immune system
Open accessAbstract
Microbial infections are recognized by the innate immune system both to elicit immediate defense and to generate long-lasting adaptive immunity. To detect and respond to vastly different groups of pathogens, the innate immune system uses several recognition systems that rely on sensing common structural and functional features associated with different classes of microorganisms. These recognition systems determine microbial location, viability, replication and pathogenicity. Detection of these features by recognition pathways of the innate immune system is translated into different classes of effector responses though specialized populations of dendritic cells. Multiple mechanisms for the induction of immune responses are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate effector responses. Here we discuss these emerging principles of innate control of adaptive immunity.
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“TLRs do not directly initiate phagocytosis but facilitate it more effectively [27].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [27]
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“In more than 400 healthy, middle to early old age participants drawn from the Whitehall II Cohort study, self-reported short sleep duration in men, but not in women, was related to shorter leukocyte telomere length”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [267]
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“Macrophages recognize microorganisms via a limited number of pattern recognition receptors, including TLRs, which play crucial roles in innate immune responses (Iwasaki and Medzhitov, 2015; Browne, 2020).”
BackgroundLeiser, O. P., Hobbs, E. C., Sims, A. M., Korch, G. W., & Taylor, K. (2021) · Pathogens · doi:10.3390/pathogens10111497 · Cited by 23
“tuned to the type, replication status, virulence, and viability of an infectious agent as well as the route of infection [27].”
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“Innate cytokines are critical for both priming and reactivation of CD4+ T cells (58, 59).”
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“Pathogen-recognition receptors expressed by the distinct subsets of DC play a major role in determining the outcome of immune responses to pathogens, by regulating the secretion of directive cytokines (19).”
BackgroundModulation of innate and adaptive immune responses by arabinoxylans
Fadel, A., Plunkett, A., Li, W., Gyamfi, V. E. T., Nyaranga, R. R., Fadel, F., Dakak, S., Ranneh, Y., Salmon, Y., & Ashworth, J. (2017) · Journal of Food Biochemistry · doi:10.1111/jfbc.12473 · Cited by 23
“The immune system consists of innate immunity, 87 which is a stereotyped rapid response to a stimulus, and adaptive immunity, which is a slower 88 but highly specific response (Iwasaki & Medzhitov, 2015).”
BackgroundVo, H. T. M., Baudner, B. C., Sammicheli, S., Iannacone, M., D’Oro, U., & Piccioli, D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00641 · Cited by 23
“DCs can express and release the activating/survival signal for B cells BAFF (36, 37) and can be stimulated by TLR7 engagement (3, 8, 35).”
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“Pattern recognition receptors (PRRs) play a sentinel role in the activation of the innate immune system by detecting pathogen associated molecular patterns (PAMPs) associated with viruses and bacteria (Iwasaki and Medzhitov, 2015).”
Suresh, M., Czerwinski, S., Murreddu, M. G., Kallakury, B., Ramesh, A., Gudima, S. O., & Menne, S. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1008248 · Cited by 23
“APCs such as dendritic cells (DCs), macrophages, and B-cells were further studied, since these cell subsets are responsible for initiating and shaping the adaptive immune response [22].”
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Mechanistic rationales for combining immunotherapy with radiotherapy
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What do primary immunodeficiencies tell us about the essentiality/redundancy of immune responses?
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Chikungunya Virus Vaccines: Platforms, Progress, and Challenges
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“DCs bridge innate immunity and adaptive immunity through their unique antigen-presenting ability (1, 2).”
BackgroundThe critical impacts of small RNA biogenesis proteins on aging, longevity and age-related diseases
Proshkina, E., Solovev, I. A., Koval, L. A., & Moskalev, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101087 · Cited by 24
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“Stimulation of innate immunity, in addition to stimulation by antigens, is crucial for the activation of antigen-presenting cells for efficient induction of acquired immunity (62).”
BackgroundERAP1 is a critical regulator of inflammasome-mediated proinflammatory and ER stress responses
Blake, M. K., O’Connell, P. M., Pepelyayeva, Y., Godbehere, S., Aldhamen, Y. A., & Amalfitano, A. (2022) · BMC Immunology · doi:10.1186/s12865-022-00481-9 · Cited by 22
“Synthesis of inflammatory cytokines and chemokines by the innate immune system is primarily initiated by activation of various germline-encoded pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs), RIG-I-like receptors (RLR), and NOD-like receptors (NLRs) [13].”
BackgroundFungal-mediated lung allergic airway disease: The critical role of macrophages and dendritic cells
Furlong-Silva, J., & Cook, P. C. (2022) · PLoS Pathogens · doi:10.1371/journal.ppat.1010608 · Cited by 23
“In the lung, DCs acquire potential allergens and migrate to the draining lymph nodes (LNs) activating antigen specific T cell responses [78,79].”
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“Most DCs exist as immature cells that typically express low levels of major histocompatibility complex II and costimulatory molecules and therefore are inclined to modulate T cell di ff erentiation towards T helper 1 (Th1), T helper 2 (Th2), T helper 17 (Th17), or regulatory T (Treg) cell [12].”
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“T-helper (Th) cells play an important role in adaptive immunity and are involved not only in host defense against different types of infectious agents, but also in pathogenesis of autoimmunity and inflammatory diseases (Paul & Zhu, 2010; Abraham & Medzhitov, 2011; Iwasaki & Medzhitov, 2015).”
Li, Y., Liu, X., Cui, Z., Zheng, Y., Jiang, H., Zhang, Y., Li, Z., Zhu, S., Chu, P. K.-H., & Wu, S. (2023) · Research · doi:10.34133/research.0096 · Cited by 22
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“Detection of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) activates multiple cell-intrinsic antimicrobial pathways, including autophagy and inflammasome assembly [3, 4], and proinflammatory signaling pathways required for coordinating protective adaptive immune responses [5, 6…”
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“Recently, it has been suggested that the innate immune system noticeably controls the adaptive defense [2] The innate immune defense includes defensins, which are small, cysteine-rich, cationic, antimicrobial peptides composed of 18e45 amino acids with molecular weights of 3e4 kDa [3].”
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“Innate immunity not only affords immediate protection against invading microbes but also instructs adaptive immunity to select a specific arm of antimicrobial effector functions (Iwasaki and Medzhitov, 2015).”
BackgroundDynamic Ligand Presentation in Biomaterials
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“As for CLRs, it has been shown that activation of DC-SIGN in DCs by different microbial compounds promotes Tregs-responses [38].”
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Metadata
- Authors
- Iwasaki, A., & Medzhitov, R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Iwasaki, Akiko
- Medzhitov, Ruslan
- Venue
- Nature Immunology
- Published
- 2015-03-19
- Volume
- 16
- Issue
- 4
- Pages
- 343-353
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC4507498
- OpenAlex
- W2044757050
- Cited by
- 2,160
- References
- 139
- Citations by year
- 2026: 183 · 2025: 212 · 2024: 181 · 2023: 193 · 2022: 204 · 2021: 239 · 2020: 216 · 2019: 189 · 2018: 187 · 2017: 167 · 2016: 157 · 2015: 31
- FWCI
- 17.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Allergy and Infectious Diseases (R01AI064705, AI062428, AI 064705, R01AI062428, AI 081884, R56AI062428, AI089771, R01AI089771, R01AI054359, R37AI046688, AI046688, R01AI081884, R01AI046688)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK071754, R01DK071754)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- innate immunity, adaptive immunity, innate-adaptive immune crosstalk, pathogen recognition, dendritic cells, cytokines, lymphocyte activation, microbial infection, pattern recognition receptors
- MeSH terms
- Animals, Bacteria, Dendritic Cells, Fungi, Gene Expression Regulation, Helminths, Humans, Immunity, Innate, Intestines, Lung, Skin, Viruses, Lymphocyte Subsets, Cytokines, Receptors, Pattern Recognition, Adaptive Immunity
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