The contribution of interleukin-12/interferon-gamma axis in protection against neonatal pulmonary Chlamydia muridarum challenge.
Neonatal Chlamydia trachomatis pneumonia has been associated with respiratory sequelae in later life. We recently established a mouse model of neonatal pulmonary Chlamydia muridaum infection and found an important contribution of IFN-gamma to protective immunity. In this study, we further characterized the role of Th1-type cytokines; IL-12, IFN-gamma, and IFN-gamma signaling using mice genetically deficient in IL-12, IFN-gamma, or IFN-gamma receptor 1. All 3 knockout (KO) mice challenged intranasally with C. muridarum 1 day after birth exhibited 100% mortality by day 17 post-challenge whereas wild-type (WT) animals survived the monitoring period of 1 month. The KO mice exhibited greater lung bacterial burdens and enhanced dissemination to the liver, compared to WT animals. The inflammatory cellular infiltration in C. muridarum-challenged KO animals was significantly reduced in the lungs, but markedly enhanced in the livers of the KO mice compared to similarly challenged WT mice. It was also found that a deficiency in IL-12 or IFN-gamma resulted in correspondingly reduced IFN-gamma or IL-12 production, respectively, suggesting an intricate interdependence in the induction of these cytokines. Collectively, these results suggest that the IL-12/ IFN-gamma axis induces pulmonary cellular infiltration, induces bacterial clearance from the lung, reduces dissemination to other organs, and promotes the survival of the host during neonatal pulmonary chlamydial infection.
Jupelli
Madhulika
M
South Texas Center for Emerging Infectious Diseases, Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249, USA.
Selby
Dale M
DM
Guentzel
M Neal
MN
Chambers
James P
JP
Forsthuber
Thomas G
TG
Zhong
Guangming
G
Murthy
Ashlesh K
AK
Arulanandam
Bernard P
BP
D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology; D023502:Chlamydia muridarum / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D015169:Colony Count, Microbial; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
D017471:Receptors, Interferon; D018664:Interleukin-12; D007371:Interferon-gamma