Critical role of Th17 responses in a murine model of Neisseria gonorrhoeae genital infection.
Host immune responses, including the characteristic influx of neutrophils, against Neisseria gonorrhoeae are poorly understood; adaptive immunity is minimal and non-protective. We hypothesize that N. gonorrhoeae selectively elicits Th17-dependent responses, which trigger innate defense mechanisms, including neutrophils and antimicrobial proteins, that it can resist. We found that N. gonorrhoeae induced the production of interleukin-17 (IL-17) in mouse T-cells and Th17-inducing cytokines in mouse and human APCs in vitro. IL-17 was induced in the iliac lymph nodes in vivo in a female mouse model of genital tract gonococcal infection. Antibody blockade of IL-17 or deletion of the major IL-17 receptor (IL-17R) in IL-17RA(KO) mice led to prolonged infection and diminished neutrophil influx. Genital tract tissue from IL-17RA(KO) mice showed reduced production of neutrophil-attractant chemokines in response to culture with N. gonorrhoeae. These results imply a crucial role for IL-17 and Th17 cells in the immune response to N. gonorrhoeae.
Feinen
B
B
Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, Buffalo, New York, USA. Feinen@buffalo.edu
Jerse
A E
AE
Gaffen
S L
SL
Russell
M W
MW
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006069:Gonorrhea / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053722:Receptors, Interleukin-17 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D000906:Antibodies; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17