Perturbation of Thymocyte Development Underlies the PRRS Pandemic: A Testable Hypothesis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F19%3A00508429" target="_blank" >RIV/61388971:_____/19:00508429 - isvavai.cz</a>
Result on the web
<a href="https://www.frontiersin.org/articles/10.3389/fimmu.2019.01077/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fimmu.2019.01077/full</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fimmu.2019.01077" target="_blank" >10.3389/fimmu.2019.01077</a>
Alternative languages
Result language
angličtina
Original language name
Perturbation of Thymocyte Development Underlies the PRRS Pandemic: A Testable Hypothesis
Original language description
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).
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30102 - Immunology
Result continuities
Project
<a href="/en/project/GA16-09296S" target="_blank" >GA16-09296S: What cells are responsible for unselected B cell repertoire in the porcine thymus?</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Frontiers in Immunology
ISSN
1664-3224
e-ISSN
—
Volume of the periodical
10
Issue of the periodical within the volume
1077
Country of publishing house
CH - SWITZERLAND
Number of pages
13
Pages from-to
1077
UT code for WoS article
000467973200001
EID of the result in the Scopus database
2-s2.0-85067095912