{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T05:18:50Z","timestamp":1718255930918},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,12,27]],"date-time":"2011-12-27T00:00:00Z","timestamp":1324944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The role of TLR signaling in linking the innate and adaptive immune systems has been a controversial issue that remains to be solved. Here, we determined whether MyD88\u2010dependent TLR signals are required for the generation of B\u2010cell responses during chronic <jats:italic>Salmonella<\/jats:italic> infection. Oral administration of recombinant attenuated <jats:italic>Salmonella enterica<\/jats:italic> serovar Typhimurium vaccine (RASV) strain in MyD88<jats:sup>\u2212\/\u2212<\/jats:sup> mice resulted in chronic infection. Infection was accompanied by enlarged germinal centers and hypergammaglobulinemia with anti\u2010double\u2010stranded DNA (dsDNA)\u2010specific Ab in sera, and the deposition of immune complexes in the kidneys, suggesting onset of autoimmunity. CD4<jats:sup>+<\/jats:sup> T cells expressing PD\u20101, CXCR5, ICOS, and IL\u201021 were dramatically increased in chronically infected mice, indicating the expansion of follicular helper T (Tfh)\u2010like cells. Of note, the depletion of CD4<jats:sup>+<\/jats:sup> T cells completely blocked the generation of polyclonal IgG Ab in sera after oral RASV challenge. Inflammatory myeloid cells expressing CD11b and Gr\u20101 accumulated in high numbers in the spleen of MyD88<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Interestingly, the blockade of PD\u20101 or ICOS significantly reduced the hypergammaglobulinemia and dsDNA\u2010specific autoantibody production. Overall, these results suggest that Tfh\u2010like cells in chronic bacterial infection trigger autoimmune hypergammaglobulinemia in a PD\u20101\u2010 and ICOS\u2010dependent manner.<\/jats:p>","DOI":"10.1002\/eji.201141748","type":"journal-article","created":{"date-parts":[[2011,11,22]],"date-time":"2011-11-22T11:25:38Z","timestamp":1321961138000},"page":"618-628","source":"Crossref","is-referenced-by-count":10,"title":["Expansion of Tfh\u2010like cells during chronic <i>Salmonella<\/i> exposure mediates the generation of autoimmune hypergammaglobulinemia in MyD88\u2010deficient 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