IL-17A/F-signaling does not contribute to the initial phase of mucosal inflammation triggered by S. Typhimurium.
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.
Institute of Microbiology, D-BIOL, ETH Zürich, Zürich, Switzerland.
Pascal
P
Songhet
Manja
M
Barthel
Till A
TA
Röhn
Laurye
L
Van Maele
Delphine
D
Cayet
Jean-Claude
JC
Sirard
Martin
M
Bachmann
Manfred
M
Kopf
Wolf-Dietrich
WD
Hardt
D000818:Animals; D002432:Cecum / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004760:Enterocolitis / Q000235:genetics / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013997:Time Factors; D014611:Vaccination / Q000379:methods
D018925:Chemokines; D016207:Cytokines; D020381:Interleukin-17; D053722:Receptors, Interleukin-17