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      The Role of Dendritic Cells During Infections Caused by Highly Prevalent Viruses

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          Abstract

          Dendritic cells (DCs) are a type of innate immune cells with major relevance in the establishment of an adaptive response, as they are responsible for the activation of lymphocytes. Since their discovery, several reports of their role during infectious diseases have been performed, highlighting their functions and their mechanisms of action. DCs can be categorized into different subsets, and each of these subsets expresses a wide arrange of receptors and molecules that aid them in the clearance of invading pathogens. Interferon (IFN) is a cytokine -a molecule of protein origin- strongly associated with antiviral immune responses. This cytokine is secreted by different cell types and is fundamental in the modulation of both innate and adaptive immune responses against viral infections. Particularly, DCs are one of the most important immune cells that produce IFN, with type I IFNs (α and β) highlighting as the most important, as they are associated with viral clearance. Type I IFN secretion can be induced via different pathways, activated by various components of the virus, such as surface proteins or genetic material. These molecules can trigger the activation of the IFN pathway trough surface receptors, including IFNAR, TLR4, or some intracellular receptors, such as TLR7, TLR9, and TLR3. Here, we discuss various types of dendritic cells found in humans and mice; their contribution to the activation of the antiviral response triggered by the secretion of IFN, through different routes of the induction for this important antiviral cytokine; and as to how DCs are involved in human infections that are considered highly frequent nowadays.

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          Most cited references255

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          NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control

          Summary Conventional type 1 dendritic cells (cDC1) are critical for antitumor immunity, and their abundance within tumors is associated with immune-mediated rejection and the success of immunotherapy. Here, we show that cDC1 accumulation in mouse tumors often depends on natural killer (NK) cells that produce the cDC1 chemoattractants CCL5 and XCL1. Similarly, in human cancers, intratumoral CCL5, XCL1, and XCL2 transcripts closely correlate with gene signatures of both NK cells and cDC1 and are associated with increased overall patient survival. Notably, tumor production of prostaglandin E2 (PGE2) leads to evasion of the NK cell-cDC1 axis in part by impairing NK cell viability and chemokine production, as well as by causing downregulation of chemokine receptor expression in cDC1. Our findings reveal a cellular and molecular checkpoint for intratumoral cDC1 recruitment that is targeted by tumor-derived PGE2 for immune evasion and that could be exploited for cancer therapy.
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            IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex.

            We report here the identification of a ligand-receptor system that, upon engagement, leads to the establishment of an antiviral state. Three closely positioned genes on human chromosome 19 encode distinct but paralogous proteins, which we designate interferon-lambda1 (IFN-lambda1), IFN-lambda2 and IFN-lambda3 (tentatively designated as IL-29, IL-28A and IL-28B, respectively, by HUGO). The expression of IFN-lambda mRNAs was inducible by viral infection in several cell lines. We identified a distinct receptor complex that is utilized by all three IFN-lambda proteins for signaling and is composed of two subunits, a receptor designated CRF2-12 (also designated as IFN-lambdaR1) and a second subunit, CRF2-4 (also known as IL-10R2). Both receptor chains are constitutively expressed on a wide variety of human cell lines and tissues and signal through the Jak-STAT (Janus kinases-signal transducers and activators of transcription) pathway. This receptor-ligand system may contribute to antiviral or other defenses by a mechanism similar to, but independent of, type I IFNs.
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              IL-28, IL-29 and their class II cytokine receptor IL-28R.

              Cytokines play a critical role in modulating the innate and adaptive immune systems. Here, we have identified from the human genomic sequence a family of three cytokines, designated interleukin 28A (IL-28A), IL-28B and IL-29, that are distantly related to type I interferons (IFNs) and the IL-10 family. We found that like type I IFNs, IL-28 and IL-29 were induced by viral infection and showed antiviral activity. However, IL-28 and IL-29 interacted with a heterodimeric class II cytokine receptor that consisted of IL-10 receptor beta (IL-10Rbeta) and an orphan class II receptor chain, designated IL-28Ralpha. This newly described cytokine family may serve as an alternative to type I IFNs in providing immunity to viral infection.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                16 July 2020
                2020
                : 11
                : 1513
                Affiliations
                [1] 1Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Instituto Milenio de Inmunología e Inmunoterapia, Pontificia Universidad Católica de Chile , Santiago, Chile
                [2] 2Departamento de Endocrinología, Facultad de Medicina, Instituto Milenio de Inmunología e Inmunoterapia, Pontificia Universidad Católica de Chile , Santiago, Chile
                Author notes

                Edited by: Allan Randrup Thomsen, University of Copenhagen, Denmark

                Reviewed by: Marina Cella, Washington University School of Medicine in St. Louis, United States; Johan Van Weyenbergh, KU Leuven, Belgium

                *Correspondence: Alexis M. Kalergis akalergis@ 123456bio.puc.cl

                This article was submitted to Viral Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2020.01513
                7378533
                32765522
                22bffde7-b732-4dfa-b8be-366f1eaee329
                Copyright © 2020 Soto, Gálvez, Andrade, Pacheco, Bohmwald, Berrios, Bueno and Kalergis.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 March 2020
                : 09 June 2020
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 332, Pages: 22, Words: 20180
                Funding
                Funded by: Instituto Millenium 10.13039/501100007397
                Funded by: Fondo Nacional de Desarrollo Científico y Tecnológico 10.13039/501100002850
                Funded by: Comisión Nacional de Investigación Científica y Tecnológica 10.13039/501100002848
                Categories
                Immunology
                Review

                Immunology
                dendritic cells,ifn,antiviral response,viruses,immune response
                Immunology
                dendritic cells, ifn, antiviral response, viruses, immune response

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