Cited by 2,160Immune Response and InflammationImmunotherapy and Immune ResponsesImmune responses and vaccinations

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Control of adaptive immunity by the innate immune system

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Iwasaki, Akiko, Medzhitov, Ruslan·2015·Nature Immunology

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Abstract

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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García‐Estévez, L., González-Martínez, S., & Moreno‐Bueno, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.784823 · Cited by 33
“At this moment, cells, such as T lymphocytes or B lymphocytes, undergo clonal expansion in order to produce an `adaptive’ response targeted against the foreign agent (66, 67).”
Background
Structure characterization of an arabinogalactan from Cynanchum atratum and its immune stimulatory activity on RAW264.7 cells
Li, N., Yang, F., Su, J., Shi, S., Ordaz-Ortíz, J. J., Cheng, X., Xiong, S., Xu, Y., Wu, J., Wang, H., et al. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.11.172 · Cited by 29
SARS-CoV-2 Variant Delta Potently Suppresses Innate Immune Response and Evades Interferon-Activated Antiviral Responses in Human Colon Epithelial Cells
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“The innate immune response instructs the adaptive response through cytokines, chemokines, and antigen presentation (14).”
Background
IL-33's role in the gut immune system: A comprehensive review of its crosstalk and regulation
Kaur, H., Kaur, G., & Ali, S. A. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121868 · Cited by 31
Nickle-cobalt alloy nanocrystals inhibit activation of inflammasomes
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“Because of their ability to stimulate T-cells, DCs act as links between innate and adaptive immunity [10, 11].”
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Mononuclear Phagocytes
Gordon, S., & Plüddemann, A. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-31696-5.00010-3 · Cited by 29
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“Th17 cell polarization is mainly driven by the STAT3 activating cytokines IL-1 and IL6, and transforming growth factor β (TGFβ) contributes by suppressing Th1 or Th2 polarization [51,52].”
Background
Beyond Antioxidation: Keap1–Nrf2 in the Development and Effector Functions of Adaptive Immune Cells
Pant, A., Dasgupta, D., Tripathi, A., & Pyaram, K. (2023) · ImmunoHorizons · doi:10.4049/immunohorizons.2200061 · Cited by 28
lncRNA JPX-Enriched Chromatin Microenvironment Mediates Vascular Smooth Muscle Cell Senescence and Promotes Atherosclerosis
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“28 Innate immune cells can recognize relevant molecules on the surface of certain microorganisms through PRRs (pattern recognition receptors), 29 ultimately resulting in the transcriptional expression of proinflammatory cytokines, type I interferons, as well as antiviral proteins.”
Design Strategies for Hyaluronic Acid-based Drug Delivery Systems in Cancer Immunotherapy
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Pathogen recognition by NK cells amplifies the pro-inflammatory cytokine production of monocyte-derived DC via IFN-γ
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Protease activity sensors noninvasively classify bacterial infections and antibiotic responses
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Rapid Downregulation of DAB2 by Toll-Like Receptor Activation Contributes to a Pro-Inflammatory Switch in Activated Dendritic Cells
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“They interact with other innate immune cells and prime adaptive immunity to determine the type, specificity, and duration of the T cell mediated immune responses (1).”
Background
Testing the resource tradeoff hypothesis for carotenoid-based signal honesty using genetic variants of the domestic canary
Koch, R. E., Staley, M., Kavazis, A. N., Hasselquist, D., Toomey, M. B., & Hill, G. E. (2019) · Journal of Experimental Biology · doi:10.1242/jeb.188102 · Cited by 28
“Antibody production in a primary response represents the ability of the innate immune system to recognize a novel antigen and induce an adaptive immune response against that antigen, while the secondary response is largely contingent on immunological memory but will also be influenced by the functional state of the in…”
Background
Development of a FRET-Based Assay for Analysis of mAbs Internalization and Processing by Dendritic Cells in Preclinical Immunogenicity Risk Assessment
Wen, Y., Cahya, S., Zeng, W., Lin, J., Wang, X., Liu, L., Malherbe, L. P., Siegel, R. W., Ferrante, A., & Kaliyaperumal, A. (2020) · The AAPS Journal · doi:10.1208/s12248-020-00444-1 · Cited by 29
NRF2 Augments Epidermal Antioxidant Defenses and Promotes Atopy
Ogawa, T., Ishitsuka, Y., Nakamura, Y., Kubota, N., Saito, A., Fujisawa, Y., Watanabe, R., Okiyama, N., Suga, Y., Roop, D. R., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000274 · Cited by 28
“immunological memory (21), including IL-1a (22) and TSLP (3).”
Background
Fasciola hepatica induces weak NETosis and low production of intra- and extracellular ROS in exposed bovine polymorphonuclear neutrophils
Peixoto, R., Silva, L. M. R., López-Osorio, S., Zhou, E., Gärtner, U., Conejeros, I., Taubert, A., & Hermosilla, C. R. (2020) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2020.103787 · Cited by 29
A Two-Step Process of Effector Programming Governs CD4+ T Cell Fate Determination Induced by Antigenic Activation in the Steady State
Opejin, A., Surnov, A., Misulovin, Z., Pherson, M., Gross, C. J., Iberg, C. A., Fallahee, I., Bourque, J., Dorsett, D., & Hawiger, D. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108424 · Cited by 29
“The current framework underlying the functions of the immune system postulates that proinflammatory signals induce immunity, whereas homeostatic conditions facilitate tolerance (Iberg et al., 2017; Iwasaki and Medzhitov, 2015; Merad et al., 2013; Pulendran, 2015; Segura and Amigorena, 2013; Steinman, 2012; Yatim et al…”
Background
ILF3 Is a Negative Transcriptional Regulator of Innate Immune Responses and Myeloid Dendritic Cell Maturation
Nazitto, R., Amon, L. M., Mast, F. D., Aitchison, J. D., Aderem, A. A., Johnson, J. S., & Diercks, A. H. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2001235 · Cited by 29
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Ernst, O., Khan, M. M., Oyler, B. L., Yoon, S. H., Sun, J., Lin, F., Manes, N. P., MacKerell, A. D., Fraser, I. D. C., Ernst, R. K., et al. (2021) · mSystems · doi:10.1128/msystems.00306-21 · Cited by 28
“The innate immune system responds rapidly to invading pathogens, sterile infection, and tissue damage and upregulates adaptive immunity (1).”
Background
Peptide-Based Vaccines in Clinical Phases and New Potential Therapeutic Targets as a New Approach for Breast Cancer: A Review
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“The mRNA vaccines induce robust immune responses that include the production of cytokines, such as interleukin-12 (IL-12) and TNF at the site of injection, which allows the development of an effective adaptive response against the codified antigen [68] (Figure 1C).”
Background
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Influential
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“Immune sensing of DNA is observed both in early innate as well as late adaptive immune responses (59, 60).”
Background
The fifth epidermal growth factor like region of thrombomodulin alleviates LPS-induced sepsis through interacting with GPR15
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“Lipopolysaccharide (LPS), a component of gram-negative bacteria membrane, causes intensive immune responses through Toll-like receptor 4 expressed on innate immune cells, including macrophages (Macs) and dendritic cells (1).”
Background
Structural characterization of a polysaccharide from Scutellaria baicalensis Georgi and its immune-enhancing properties on RAW264.7 cells
Xiong, S., Li, N., Shi, S., Zhao, Y., Chen, J., Ruan, M., Xu, Y., Liu, R., Wang, S., & Wang, H. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.137890 · Cited by 27
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“IL-12, produced by APCs in response to microbial infection, activates NK, CD4, and CD8 T cells and promotes TH1 differentiation and IFN-g production (1).”
BackgroundInfluential
Neonatal vaccine effectiveness and the role of adjuvants
Sakala, I. G., Eichinger, K. M., & Petrovsky, N. (2019) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2019.1642748 · Cited by 29
“This is reflected in increased activity of suppressive T regulatory cells [29, 30] , reduced antigen-presenting cell (APC) function, a higher threshold for B cell activation, reduced production of immune effectors such as inflammatory cytokines, and a bias to a T helper type 2 (Th2) phenotype [31] .”
Background
TNF-α-Producing Cryptococcus neoformans Exerts Protective Effects on Host Defenses in Murine Pulmonary Cryptococcosis
Fa, Z., Xu, J., Yi, J., Sang, J., Pan, W., Xie, Q., Yang, R., Fang, W. Y., Liao, W., & Olszewski, M. A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01725 · Cited by 27
“In keeping with previous findings, direct TNF-α production by yeast strain modulated Th1/Th2 balance during infection, and drove the improved co-stimulatory activation of CD103+ cDC1, reported to be specialized in promoting Th1 response (38).”
Result
A Multiple Antigen Peptide Vaccine Containing CD4 + T Cell Epitopes Enhances Humoral Immunity against Trichinella spiralis Infection in Mice
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“Given the importance of innate immune signals in shaping adaptive immune responses [60], a particular innate immune pathway with Tfh cell-skewing ability, such as TLR8, has 10 Journal of Immunology Research been identi ﬁ ed for the rational design of Tfh cell-targeted vaccine adjuvants [61].”
Characterization of four subtypes in morphologically normal tissue excised proximal and distal to breast cancer
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“for optimal antibody responses to T-dependent antigens (34, 35).”
Background
TNF-α sculpts a maturation process in vivo by pruning tolerogenic dendritic cells
Iberg, C. A., Bourque, J., Fallahee, I., Son, S., & Hawiger, D. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110657 · Cited by 27
“The pro-immunogenic maturation of cDCs abrogates their tolerogenic functions, but how this happened was unclear (Cabeza-Cabrerizo et al., 2021; Dalod et al., 2014; Iberg et al., 2017; Iwasaki and Medzhitov, 2015; Mellman, 2013; Steinman et al., 2003a).”
BackgroundInfluential
Immune homeostasis and disorder in the testis – Roles of Sertoli cells
Chen, R., Wang, F., Chen, Y., & Han, D. (2022) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2022.103625 · Cited by 27
Induction of natural IgE by glucocorticoids
Lim, J., Lin, E. V., Hong, J. Y., Vaidyanathan, B., Erickson, S. A., Annicelli, C., & Medzhitov, R. M. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20220903 · Cited by 27
“Unlike type 1 immunity, which deals with pathogens such as bacteria and viruses, type 2 immunity defends the body from macroparasites, noxious chemicals, and toxins (Iwasaki and Medzhitov, 2015; Palm et al., 2012).”
BackgroundSelf-citation

Authors: Iwasaki, A., & Medzhitov, R.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Iwasaki, Akiko
Medzhitov, Ruslan
ORCID: Iwasaki, Akiko
Medzhitov, Ruslan
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2015-03-19
Volume: 16
Issue: 4
Pages: 343-353
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni.3123
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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Control of adaptive immunity by the innate immune system

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