title: The contribution of interleukin-12/interferon-gamma axis in protection against neonatal pulmonary Chlamydia muridarum challenge.
abstract: 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.
authors.affiliation: South Texas Center for Emerging Infectious Diseases, Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249, USA.
authors.forename: Madhulika
authors.initials: M
authors.lastname: Jupelli
authors.forename: Dale M
authors.initials: DM
authors.lastname: Selby
authors.forename: M Neal
authors.initials: MN
authors.lastname: Guentzel
authors.forename: James P
authors.initials: JP
authors.lastname: Chambers
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Forsthuber
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
authors.forename: Ashlesh K
authors.initials: AK
authors.lastname: Murthy
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
mesh_terms: 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
chemical_list: D017471:Receptors, Interferon; D018664:Interleukin-12; D007371:Interferon-gamma