IL-17A is produced by Th17, gammadelta T cells and other CD4- lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearance.
T(h)17 cells represent a new pro-inflammatory T(h) cell lineage distinct from T(h)1 and T(h)2 cells. T(h)17 cells have been shown to be involved in extracellular bacterial infection but their role in intracellular infection remains unclear. We found antigen-specific IL-17A production during a systemic infection of mice with the facultative intracellular bacterium Salmonella enterica serovar Enteritidis (S. Enteritidis) and examined the function and cellular source of IL-17A during the adaptive immune response to S. Enteritidis. Infected IL-17A-/- mice survived completely after inoculation with the highest infection dose found to be sub-lethal for wild-type (WT) C57BL/6 mice. However, at 20 and 80 days post-infection (d.p.i.), we repeatedly found mildly elevated bacterial burden in spleen and liver of IL-17A-/- mice as compared with WT mice. Overall, IL-17A-/- mice showed reduced clearance of S. Enteritidis. S. Enteritidis-specific IL-17A production was induced in splenocytes and lymph node cells of infected WT mice at both time points, 20 and 80 d.p.i. Classical CD4+ T(h)17 cells developed upon infection with Salmonella. CD4- gammadelta TCR+ and CD4- gammadelta TCR- cells were found to be additional IL-17A-producing cell populations. In infected IL-17A-/- mice, a normal T(h)1 cytokine profile was observed consistent with the overall subtle phenotype. Nevertheless, in the absence of IL-17A, recruitment of neutrophils and delayed-type hypersensitivity (DTH) reactivity was significantly compromised. Our data indicate that IL-17A responses are induced by Salmonella and mildly contribute to protective immunity during S. Enteritidis infection. Thus, IL-17A complements the IL-12/IFN-gamma axis which is essential for protective immunity against salmonellosis in mice and men.
Schulz
Silke M
SM
Institute of Immunology, College of Veterinary Medicine, University of Leipzig, An den Tierkliniken 11, 04103 Leipzig, Germany.
Köhler
Gabriele
G
Holscher
Christoph
C
Iwakura
Yoichiro
Y
Alber
Gottfried
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D015169:Colony Count, Microbial; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D012477:Salmonella enteritidis / Q000302:isolation & purification / Q000472:pathogenicity*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism*
D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta