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Cross Talk between inhibitory immunoreceptor Tyrosine-Based Activation Motif-Signaling and Toll-Like Receptor Pathways in Macrophages and Dendritic Cells
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SYSNO ASEP 0475302 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Cross Talk between inhibitory immunoreceptor Tyrosine-Based Activation Motif-Signaling and Toll-Like Receptor Pathways in Macrophages and Dendritic Cells Author(s) Hirsch, Ivan (UOCHB-X) ORCID, RID
Janovec, Václav (UOCHB-X) ORCID, RID
Stranska, R. (FR)
Bendriss-Vermare, N. (FR)Article number 394 Source Title Frontiers in Immunology. - : Frontiers Media - ISSN 1664-3224
Roč. 8, Apr 7 (2017)Number of pages 12 s. Language eng - English Country CH - Switzerland Keywords plasmacytoid dendritic cell ; conventional dendritic cells ; macrophage ; toll-like receptors ; regulatory receptors Subject RIV EC - Immunology OECD category Immunology Institutional support UOCHB-X - RVO:61388963 UT WOS 000398418100002 EID SCOPUS 85018435074 DOI 10.3389/fimmu.2017.00394 Annotation The innate immune cells sense microbial infection and self-ligands by pathogen recognition receptors (PRRs), such as toll-like receptors (TLRs) and regulatory receptors (RRs), associated with immunoreceptor tyrosine-based activation motif (ITAM). Rapid activation and concerted action of PRRs signaling and feedback inhibitory mechanisms must be engaged to ensure the host defense functions and to prevent cytotoxicity associated with excessive activation. ITAM-associated RRs can generate stimulatory or, paradoxically, inhibitory signals. The network of ITAM-associated RR, together with TLR-signaling pathways, are responsible for immunogenic or tolerogenic responses of macrophages and dendritic cells to their microenvironment. In macrophages, TLR4 signaling is inhibited by low-avidity ligation of ITAM-associated receptors, while high-avidity ligation of ITAM-associated receptors results in potentiation of TLR4 signaling together with resistance to extracellular cytokine microenvironment signals. In contrast to macrophages, TLR7/9 signaling in plasmacytoid DCs (pDCs) is inhibited by high-avidity ligation of ITAM-associated RR, while low-avidity ligation does not show any effect. Surprisingly, interference of ITAM-associated receptor signaling with TLR pathways has not been reported in conventional dendritic cells. Here, we present an overview of molecular mechanisms acting at the crossroads of TLR and ITAM-signaling pathways and address the question of how the high-avidity engagement of the ITAM-associated receptors in pDCs inhibits TLR7/9 signaling. Cellular context and spatiotemporal engagement of ITAM-and TLR-signaling pathways are responsible for different outcomes of macrophage versus pDC activation. While the cross-regulation of cytokine and TLR signaling, together with antigen presentation, are the principal functions of ITAM-associated RR in macrophages, the major role of these receptors in pDCs seems to be related to inhibition of cytokine production and reestablishment of a tolerogenic state following pDC activation. Pharmacologic targeting of TLR and ITAM signaling could be an attractive new therapeutic approach for treatment of chronic infections, cancer, and autoimmune and inflammatory diseases related to pDCs. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434 Year of Publishing 2018 Electronic address http://journal.frontiersin.org/article/10.3389/fimmu.2017.00394/full
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