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Perturbation of Thymocyte Development Underlies the PRRS Pandemic: A Testable Hypothesis
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SYSNO ASEP 0508429 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Perturbation of Thymocyte Development Underlies the PRRS Pandemic: A Testable Hypothesis Tvůrce(i) Butler, J. E. (US)
Šinkora, Marek (MBU-M) RID, ORCID
Wang, G. (CN)
Štěpánová, Kateřina (MBU-M) ORCID
Li, Y. (CN)
Cai, X. (CN)Číslo článku 1077 Zdroj.dok. Frontiers in Immunology. - : Frontiers Media - ISSN 1664-3224
Roč. 10, č. 1077 (2019)Poč.str. 13 s. Jazyk dok. eng - angličtina Země vyd. CH - Švýcarsko Klíč. slova hypergammaglobulinemia ; PRRS virus ; T cell repertoire Vědní obor RIV EC - Imunologie Obor OECD Immunology CEP GA16-09296S GA ČR - Grantová agentura ČR Způsob publikování Open access Institucionální podpora MBU-M - RVO:61388971 UT WOS 000467973200001 EID SCOPUS 85067095912 DOI 10.3389/fimmu.2019.01077 Anotace Porcine reproductive and respiratory syndrome virus (PRRSV) causes immune dysregulation during the Critical Window of Immunological Development. We hypothesize that thymocyte development is altered by infected thymic antigen presenting cells (TAPCs) in the fetal/neonatal thymus that interact with double-positive thymocytes causing an acute deficiency of T cells that produces ´holes´ in the T cell repertoire allowing for poor recognition of PRRSV and other neonatal pathogens. The deficiency may be the result of random elimination of PRRSV-specific T cells or the generation of T cells that accept PRRSV epitopes as self-antigens. Loss of helper T cells for virus neutralizing (VN) epitopes can result in the failure of selection for B cells in lymph node germinal centers capable of producing high affinity VN antibodies. Generation of cytotoxic and regulatory T cells may also be impaired. Similar to infections with LDV, LCMV, MCMV, HIV-1 and trypanosomes, the host responds to the deficiency of pathogen-specific T cells and perhaps regulatory T cells, by ´last ditch´ polyclonal B cell activation. In colostrum-deprived PRRSV-infected isolator piglets, this results in hypergammaglobulinemia, which we believe to be a ´red herring´ that detracts attention from the thymic atrophy story, but leads to our second independent hypothesis. Since hypergammaglobulinemia has not been reported in PRRSV-infected conventionally-reared piglets, we hypothesize that this is due to the down-regulatory effect of passive maternal IgG and cytokines in porcine colostrum, especially TGF beta which stimulates development of regulatory T cells (Tregs). Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2020 Elektronická adresa https://www.frontiersin.org/articles/10.3389/fimmu.2019.01077/full
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