IL-17A-F-signaling does not contribute to the initial phase of mucosal inflammation triggered by S. Typhimurium.Report as inadecuate




IL-17A-F-signaling does not contribute to the initial phase of mucosal inflammation triggered by S. Typhimurium. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 ETH Zürich - Eidgenössische Technische Hochschule Zürich 2 Cytos Biotechnology 3 CIL - Centre d-infection et d-immunité de Lille 4 Institute of Integrative Biology, Molecular Biomedicine

Abstract : Salmonella enterica subspecies 1 serovar Typhimurium S. Typhimurium causes diarrhea and acute inflammation of the intestinal mucosa. The pro-inflammatory cytokines IL-17A and IL-17F are strongly induced in the infected mucosa but their contribution in driving the tissue inflammation is not understood. We have used the streptomycin mouse model to analyze the role of IL-17A and IL-17F and their cognate receptor IL-17RA in S. Typhimurium enterocolitis. Neutralization of IL-17A and IL-17F did not affect mucosal inflammation triggered by infection or spread of S. Typhimurium to systemic sites by 48 h p.i. Similarly, Il17ra- mice did not display any reduction in infection or inflammation by 12 h p.i. The same results were obtained using S. Typhimurium variants infecting via the TTSS1 type III secretion system, the TTSS1 effector SipA or the TTSS1 effector SopE. Moreover, the expression pattern of 45 genes encoding chemokines-cytokines including CXCL1, CXCL2, IL-17A, IL-17F, IL-1α, IL-1β, IFNγ, CXCL-10, CXCL-9, IL-6, CCL3, CCL4 and antibacterial molecules was not affected by Il17ra deficiency by 12 h p.i. Thus, in spite of the strong increase in Il17a-Il17f mRNA in the infected mucosa, IL-17RA signaling seems to be dispensable for eliciting the acute disease. Future work will have to address whether this is attributable to redundancy in the cytokine signaling network.





Author: Pascal Songhet - Manja Barthel - Till A Röhn - Laurye Van Maele - Delphine Cayet - Jean-Claude Sirard - Martin Bachmann - Manfre

Source: https://hal.archives-ouvertes.fr/



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