Critical role of Th17 responses in a murine model of Neisseria gonorrhoeae genital infection

B. Feinen; A. E. Jerse; S. L. Gaffen; M. W. Russell

doi:10.1038/mi.2009.139

Critical role of Th17 responses in a murine model of Neisseria gonorrhoeae genital infection

B. Feinen^*, A. E. Jerse, S. L. Gaffen, M. W. Russell

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

114 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	312-321
Number of pages	10
Journal	Mucosal Immunology
Volume	3
Issue number	3
DOIs	https://doi.org/10.1038/mi.2009.139
State	Published - May 2010
Externally published	Yes

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10.1038/mi.2009.139

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title = "Critical role of Th17 responses in a murine model of Neisseria gonorrhoeae genital infection",

abstract = "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.",

author = "B. Feinen and Jerse, {A. E.} and Gaffen, {S. L.} and Russell, {M. W.}",

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AU - Feinen, B.

AU - Jerse, A. E.

AU - Gaffen, S. L.

AU - Russell, M. W.

PY - 2010/5

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N2 - 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.

AB - 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.

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