IL-23 induces IL-22 and IL-17 production in response to Chlamydia muridarum genital tract infection, but the absence of these cytokines does not influence disease pathogenesis.
OBJECTIVE
Chlamydia trachomatis infections are a significant cause of reproductive tract pathology. Protective and pathological immune mediators must be differentiated to design a safe and effective vaccine.


METHODS
Wild-type mice and mice deficient in IL-22 and IL-23 were infected intravaginally with Chlamydia muridarum, and their course of infection and oviduct pathology were compared. Local genital tract and draining lymph node immune responses were also examined in IL-23-deficient mice.


RESULTS
IL-22- and IL-23-deficient mice exhibited normal susceptibility to infection and oviduct pathology. IL-23 was required for the development of a Chlamydia-specific Th17 response in the lymph nodes and for production of IL-22 and IL-17 in the genital tract. However, influx of Th1 and innate immune cells was not compromised in the absence of IL-23.


CONCLUSIONS
IL-22 and IL-23 play either redundant or minimal roles in the pathogenesis of Chlamydia infection in the mouse model. Induction of Th17-associated cytokines by a Chlamydia vaccine should be avoided as these responses are not central to resolution of infection and have pathologic potential.
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
Lauren C
LC
Frazer
Amy M
AM
Scurlock
Matthew A
MA
Zurenski
Melissa M
MM
Riley
Margaret
M
Mintus
Derek A
DA
Pociask
Jeanne E
JE
Sullivan
Charles W
CW
Andrews
Toni
T
Darville
D000818:Animals; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D023502:Chlamydia muridarum / Q000276:immunology*; D005260:Female; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D053759:Interleukin-23 / Q000172:deficiency / Q000276:immunology*; D007378:Interleukins / Q000096:biosynthesis* / Q000172:deficiency / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010057:Oviducts / Q000276:immunology / Q000473:pathology; D060737:Reproductive Tract Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D000097043:Interleukin-22
D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D000097043:Interleukin-22
Immunopathology; Th17; intracellular bacteria