Trends in Immunology
OpinionInnate antiviral immunity: how prior exposures can guide future responses
Section snippets
Intrinsic innate antiviral immunity: a baseline defense against viral infections
Several cellular components of the innate immune system play a primary role in shaping protective and/or deleterious immune responses to infections and vaccination. Innate immune cells have traditionally included monocytes/macrophages, dendritic cells (DCs), natural killer (NK) cells, neutrophils, and granulocytes, although several cell types (including epithelial cells) can mount innate antiviral responses [1]. During an acute tissue infection, neutrophils followed by monocytes/macrophages and
Trained immunity and IIAVI: linking the future to the past
Linked with the concept of IIAVI is the recently described state of trained immunity (TI), or the acquisition of epigenetic modifications that induce a state of hyper- or hypo-responsiveness to future infection. TI was first described in monocytes/macrophages and considered ‘innate memory’ analogous to the adaptive memory seen in T and B cells (Figure 1) [16., 17., 18.]. The most well characterized example of TI involves Toll-like receptor 4 (TLR4) activation and Bacillus–Calmette–Guerin (BCG)
Daily exposure: how our history of environmental and microbial exposure shapes immunity
Exposure to a myriad of environmental agents can potentially impact antiviral immune responses (Figure 2, Key figure). Among the most important of these agents are metabolites derived from the diet and/or the microbiome. Many biological and cellular processes rely on metabolites derived from the activity of microbes on mucosal surfaces, mainly in the gastrointestinal (GI) tract. These microbes (e.g., bacteria) take breakdown products of the diet and digestion and convert them into bioactive
From metabolite to mechanism: metabolite regulation of innate immunity in response to infection or vaccination
Gut microbiota can release several metabolites, including short-chain fatty acids (SCFAs), polyamines, indoles, bile acids (BAs), and lipid-associated metabolites [24]. These metabolites bind to receptors on mammalian immune cells: NOD-like receptors [25], TLRs [26], the aryl hydrocarbon receptor (AHR) [27], and G-protein-coupled receptors (GPCRs) [28] including GPR43 [29] and GPR41 [30]. SCFAs can promote cytokine and chemokine secretion leading to migration and activation of cells such as
AHR can integrate host, microbial, and xenobiotic metabolites to modulate innate and adaptive immune responses
One of the major signaling cascades linking metabolites to immune function is the AHR [48] (Figure 3 and Box 1). AHR signaling can regulate the differentiation and function of mouse and human myeloid and plasmacytoid DCs, which are central components in generating effective immune responses to viral infection and vaccination [49,50]. However, there are conflicting reports showing that AHR can increase or decrease expression of MHC-II (which presents antigen to T cells) and CD86 which binds to
Concluding remarks and future perspectives
The emergence of epigenetics as a long-term regulator of gene expression profiles, and the capacity for metabolites derived from microbial products to impact epigenetic pathways in both innate and adaptive immune cells, suggest that differences in the microbiome/metabolome among individuals can have durable impacts on host immune responses to infection and vaccination [17]. In this opinion article we argue that new evidence suggests that the metabolome/metabotype may directly control innate
Acknowledgments
R.P.S. and J.A.T. were supported by funds from the National Cancer Institute (NCI)/National Institutes of Health (NIH) U54CA260563 and the National Institute of Allergy and Infectious Diseases (NIAID)/NIH R01AI125202, U19AI128910, and 75N93019C00046 (NIAID Adjuvant Discovery Program). M.S.S. was supported with funds from NIAID/NIH R56AI147623, U19AI057266, U19AI090023, U54CA260563, and 75N93021C00017 (NIAID Centers of Excellence for Influenza Research and Surveillance). M.S.D. was supported by
Author contributions
J.A.T. and R.P.S. conceptually developed, wrote, and edited the article. M.S.S. and M.S.D. assisted with writing and editing.
Declaration of interests
The authors declare no conflicts of interest.
Glossary
- Aryl hydrocarbon receptor (AHR)
- a cellular receptor for multiple classes of host- and microbe-derived metabolites. Activated AHR can function as a transcription factor, binding individually or cooperatively with other immune transcription factors such as NF-κB and STATs to target DNA sequences and modulate gene expression.
- Breadth
- refers to the degree of diversity in antigenic recognition of the antibody repertoire of an individual. The greater the breadth to a pathogen, the more pathogenic
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2023, Jornal de PediatriaCitation Excerpt :This phenomenon was named “trained immunity” in 2011 by Netea et al. and consists of the capacity to generate an increased response of the innate immune system to a second infection caused by the same microorganism or by a different agent (cross- or heterologous protection).2 The exact mechanisms involved in the memory of innate immunity are not known, but there is current evidence that innate immunity is modulated by the history of individual exposure to infections, immunizations, and microbial metabolites, which can either stimulate or impair the immune response.26 Stimuli to the innate response, such as infectious agents or vaccines, promote epigenetic alterations, in a type of cell reprogramming by acetylation or methylation of histones in specific genes, modifying the transcriptional profile of NK cells and macrophages, with changes in their functional phenotypes and in the expression of cell surface molecules, activating PRRs and cytokine receptors.18,26,27
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