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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BackgroundInfluential
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Shan, C., Xiong, Y., Miao, F., Liu, T., Akhtar, R. W., Shah, S. A. H., Gao, H., Zhu, E., & Cheng, Z. (2023) · Poultry Science · doi:10.1016/j.psj.2023.102582 · Cited by 15
Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses
Giessler, K. S., Goehring, L. S., Jacob, S. I., Davis, A., Esser, M. M., Lee, Y., Zarski, L. M., Weber, P. S. D., & Hussey, G. S. (2024) · Journal of General Virology · doi:10.1099/jgv.0.001987 · Cited by 17
Bacterial Infections in Acute-on-chronic Liver Failure: Epidemiology, Diagnosis, Pathogenesis, and Management
Xu, Z., Zhang, X., Chen, J., Shi, Y., & Ji, S.-W. (2024) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2024.00137 · Cited by 15
“47,49 Furthermore, bacteria and their by-products can cause indirect tissue damage by triggering systemic inflammatory responses that affect circulatory function, potentially resulting in organ damage due to oxidative stress, reduced organ perfusion, and endothelial dysfunction.”
Background
CO-DELIVERY of glutamic acid-extended peptide antigen and imidazoquinoline TLR7/8 agonist via ionizable lipid nanoparticles induces protective anti-tumor immunity
Ye, T., Zhong, Z., Cappellesso, F., Deswarte, K., Chen, Y., Lauwers, H., Lombaerde, E. D., Gontsarik, M., Lienenklaus, S., Lysebetten, D. V., et al. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122693 · Cited by 14
Coumarin derivatives ameliorate the intestinal inflammation and pathogenic gut microbiome changes in the model of infectious colitis through antibacterial activity
Jung, H.-S., Park, Y., Gu, B., Han, G., Ji, W., Hwang, S. M., & Kim, M. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1362773 · Cited by 17
“Changes in innate immunity, such as monocyte response, can affect T cell immunity during pathogen infection (Iwasaki and Medzhitov, 2015).”
Background
Insights into the pathogenesis of gestational and hepatic diseases: the impact of ferroptosis
You, Y., Qian, Z., Jiang, Y., Chen, L., Wu, D., Liu, L., Zhang, F., Ning, X., Zhang, Y., & Xiao, J. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1482838 · Cited by 18
“The adaptive immune system, on the other hand, involves T and B lymphocytes along with natural killer (NK) cells, which provide a more speci ﬁ c and targeted response to pathogens (Iwasaki and Medzhitov, 2015).”
Understanding immune system dysfunction and its context in mood disorders: psychoneuroimmunoendocrinology and clinical interventions
Ortega, M. A., Fraile‐Μartinez, O., Montero, C. G., Díaz, R., López-González, L., Monserrat, J., Barrena-Blázquez, S., Álvarez-Mon, M. Á., Lahera, G., & Álvarez‐Mon, M. (2024) · Military Medical Research · doi:10.1186/s40779-024-00577-w · Cited by 21
“Adaptative immunity provides broader and highly specific responses after recognition for both self-and nonself-anti-gens by the action of antigen-presenting cells (APCs), mainly dendritic cells [48].”
Antibiotic induced bacterial lysis provides a reservoir of persisters
Podlesek, Z., Butala, M., Šakanović, A., & Žgur‐Bertok, D. (2016) · Antonie van Leeuwenhoek · doi:10.1007/s10482-016-0657-x · Cited by 15
“…is of high medical significance as inevitably, at bacterial infection sites, antibiotic treatment or host responses that can kill bacteria (Iwasaki and Medzhitov 2015), may provoke entrapment of a substantial proportion of live bacterial cells within the compact debris that could elicit…”
Background
Engystol reduces onset of experimental respiratory syncytial virus-induced respiratory inflammation in mice by modulating macrophage phagocytic capacity
Wronski, S., Dannenmaier, J., Schild, S., Macke, O., Müller, L., Burmeister, Y., Seilheimer, B., & Müller, M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0195822 · Cited by 15
Duplication of toll-like receptor 22 in teleost fishes
Qi, D., Yan, C., Zhang, C., Wang, Z., Wang, W., Chen, Q., Zheng, Z., & Zhang, Z. (2019) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2019.09.067 · Cited by 15
Comprehensive co‑expression analysis reveals TMC8 as a prognostic immune‑associated gene in head and neck squamous cancer
Lin, B., Wang, S., Yao, Y., Shen, Y., & Yang, H. (2021) · Oncology Letters · doi:10.3892/ol.2021.12759 · Cited by 15
“However, different subpopulations of lymphocytes exert different effects (47,48), and whether the expression of TMC8 can reflect the enrichment of specific subpopulations has not yet been reported to the authors' knowl‐ edge.”
Novel Immunomodulatory Therapies for Respiratory Pathologies
Tavares, L. P., Galvão, I., & Ferrero, M. R. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00073-6 · Cited by 19
Immunoinformatic Approaches for Vaccine Designing for Pathogens with Unclear Pathogenesis
Arora, N., Keshri, A. K., Kaur, R., Rawat, S. S., & Prasad, A. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1892-9_22 · Cited by 14
HuR keeps interferon‐β mRNA stable
Takeuchi, O. (2015) · European Journal of Immunology · doi:10.1002/eji.201545616 · Cited by 15
Does antiparasite behavior improve with experience? An experimental test of the priming hypothesis
Villa, S. M., Campbell, H. E., Bush, S. E., & Clayton, D. H. (2016) · Behavioral Ecology · doi:10.1093/beheco/arw032 · Cited by 15
“tial exposure often primes the immune system, allowing it to rapidly recognize and fight subsequent infections (Klein 1982; Siva-Jothy et al. 2005; Iwasaki and Medzhitov 2015).”
Background
c-Jun integrates signals from both MEK/ERK and MKK/JNK pathways upon vaccinia virus infection
Leite, F. G. G., Torres, A. A., de Oliveira, L. C., da Cruz, A. F. P., Soares-Martins, J. A. P., Pereira, A. C. T. D. C., Trindade, G. D. S., Abrahão, J. S., Kroon, E. G., Ferreira, P. C. P., et al. (2017) · Archives of Virology · doi:10.1007/s00705-017-3446-6 · Cited by 15
Interleukin 1α (IL-1α) Promotes Pathogenic Immature Myeloid Cells and IL-1β Favors Protective Mature Myeloid Cells During Acute Lung Infection
Periasamy, S., & Harton, J. A. (2018) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiy049 · Cited by 15
“However, B and T cells are essential for the development of protective, adaptive immunity [44] and thus might be important for resistance.”
Background
Host immune response–inspired development of the influenza vaccine
Choi, A., García‐Sastre, A., & Schotsaert, M. (2020) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2020.04.008 · Cited by 15
Myeloid dysregulation and therapeutic intervention in COVID-19
Gu, R., Mao, T., Qiao, L., Su, T. T., & Wang, J. (2021) · Seminars in Immunology · doi:10.1016/j.smim.2021.101524 · Cited by 14
“After detection of viral infection through PAMP or DAMP sensing, innate sensors rapidly trigger the production of cytokines and chemokines to initiate antiviral innate and adaptive immunity [26].”
Complementary role of transcriptomic endotyping and protein-based biomarkers for risk stratification in sepsis-associated acute kidney injury
Tavris, B. S., Morath, C. P., Rupp, C., Szudarek, R., Uhle, F., Sweeney, T. E., Liesenfeld, O., Fiedler, M. O., Dubler, S., Zeier, M., et al. (2025) · Critical Care · doi:10.1186/s13054-025-05361-3 · Cited by 19
“Adaptive immunity is known to be activated during prolonged sepsis, driven by damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) released during innate immune activation [35–37].”
Dietary fiber derived short-chain fatty acids as a critical driver of the gut–bone axis in animal bone health: A review
Zulfiqar, Z., Huang, S., & Shi, Y. (2025) · Animal nutrition · doi:10.1016/j.aninu.2025.05.002 · Cited by 17
Hop-derived fraction rich in beta acids and prenylflavonoids regulates the inflammatory response in dendritic cells differently from quercetin: unveiling metabolic changes by mass spectrometry-based metabolomics
Sommella, E., Verna, G., Liso, M., Salviati, E., Esposito, T., Carbone, D., Pecoraro, C., Chieppa, M., & Campiglia, P. (2021) · Food & Function · doi:10.1039/d1fo02361f · Cited by 15
Beyond the gastric epithelium — the paradox of Helicobacter pylori-induced immune responses
Neuper, T., Frauenlob, T., Posselt, G., & Horejs‐Hoeck, J. (2022) · Current Opinion in Immunology · doi:10.1016/j.coi.2022.102208 · Cited by 14
Drosophila Toll-9 is induced by aging and neurodegeneration to modulate stress signaling and its deficiency exacerbates tau-mediated neurodegeneration
Sakakibara, Y., Yamashiro, R., Chikamatsu, S., Hirota, Y., Tsubokawa, Y., Nishijima, R., Takei, K., Sekiya, M., & Iijima, K. (2023) · iScience · doi:10.1016/j.isci.2023.105968 · Cited by 14
“INTRODUCTION Host immune responses against infection belong to either innate or adaptive immunity.(1,2) Processes underlying adaptive immunity only exist in vertebrates,(3,4) whereas innate immunity, a rapid and efficient defense mechanism that detects pathogen-associated molecular patterns through a set of pathogen r…”
Background
Orchestration of inflammation in contact allergy by innate immune and cellular stress responses
Martin, S. F., Rühl‐Muth, A., & Esser, P. R. (2023) · Allergo Journal International · doi:10.1007/s40629-023-00275-4 · Cited by 15
“It is essential for the activation of tissue repair and regeneration [5, 6] and for the initiation of immune responses [7].”
Host immune responses against African swine fever virus: Insights and challenges for vaccine development
Orosco, F. L. (2023) · Open Veterinary Journal · doi:10.5455/ovj.2023.v13.i12.2 · Cited by 18
“This recognition triggers innate immunity, culminating in the induction of proinflammatory cytokines and type I interferons (IFNs) to coordinate innate immunity (Iwasaki and Medzhitov, 2015), as illustrated in Figure 3.”
Background
Mechanical communication and function regulation of immune cells
Chen, Y., Xie, R., Cao, T., Zhang, Y., Wang, X., Xu, Y., Fan, Q., & Ye, F. (2024) · Fundamental Research · doi:10.1016/j.fmre.2024.04.008 · Cited by 14
Microbiota‐immune‐brain interactions: A new vision in the understanding of periodontal health and disease
Breivik, T. J., Gjermo, P. E., Gundersen, Y., Opstad, P. K., Murison, R. C. C., Hugoson, A., von Hörsten, S., & Fristad, I. (2024) · Periodontology 2000 · doi:10.1111/prd.12610 · Cited by 15
“93,94 When Th0 cells receive information about pathogenic bacteria and fungi that have not infected tissue cells (extracellular microbes), but that have the potential to do so, they produce and secrete other types of pro-inflammatory cytokines (interleukin; IL-17 and IL-22).”
Inhibitory effect of saliva on osteoclastogenesis in vitro requires toll-like receptor 4 signaling
Müller, H., Caballé‐Serrano, J., Lussi, A., & Gruber, R. (2017) · Clinical Oral Investigations · doi:10.1007/s00784-016-2041-7 · Cited by 14
“tential beneficial effects related to the innate immune system, which is triggered by the activation of the pattern recognition receptors—including TLR4 [34].”
Administration of plasmacytoid dendritic cell-stimulative lactic acid bacteria enhances antigen-specific immune responses
Suzuki, H., Jounai, K., Ohshio, K., Fujii, T., & Fujiwara, D. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.07.042 · Cited by 14
Inflammation and Depression: the Neuroimmune Connection
Toups, M. S. P. (2018) · Current Treatment Options in Psychiatry · doi:10.1007/s40501-018-0157-x · Cited by 13
Ontogeny of cytokine responses to PHA from birth to adulthood
Jeljeli, M. M., Guérin, V., Pédron, B., Gressèns, P., Sibony, O., & Sterkers, G. (2019) · Pediatric Research · doi:10.1038/s41390-019-0383-y · Cited by 14
An agonistic anti‐Toll‐like receptor 4 monoclonal antibody as an effective adjuvant for cancer immunotherapy
Tsukamoto, H., Kubota, K., Shichiku, A., Maekawa, M., Mano, N., Yagita∥, H., Ohta, S., & Tomioka, Y. (2019) · Immunology · doi:10.1111/imm.13095 · Cited by 14
Innate Immune Defense in the Male Reproductive System and Male Fertility
Wang, F., Chen, R., & Han, D. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.89346 · Cited by 16
A secreted pore‐forming protein modulates cellular endolysosomes to augment antigen presentation
Deng, C., Liu, L., Liu, L., Wang, Q., Guo, X., Lee, W., Li, S., & Zhang, Y. (2020) · The FASEB Journal · doi:10.1096/fj.202001176r · Cited by 13
Amphiphilic desmuramyl peptides for the rational design of new vaccine adjuvants: Synthesis, in vitro modulation of inflammatory response and molecular docking studies
Khan, F., Nasim, N., Wang, Y., Alhazmi, A., Sanam, M., Ul‐Haq, Z., Damayanthi, Y., Ulanova, M., & Jiang, Z. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112863 · Cited by 14
Targeted Nanophotoimmunotherapy Potentiates Cancer Treatment by Enhancing Tumor Immunogenicity and Improving the Immunosuppressive Tumor Microenvironment
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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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