TY - JOUR
T1 - The contribution of interleukin-12/interferon-γ axis in protection against neonatal pulmonary chlamydia muridarum challenge
AU - Jupelli, Madhulika
AU - Selby, Dale M.
AU - Guentzel, M. Neal
AU - Chambers, James P.
AU - Forsthuber, Thomas G.
AU - Zhong, Guangming
AU - Murthy, Ashlesh K.
AU - Arulanandam, Bernard P.
PY - 2010/6/1
Y1 - 2010/6/1
N2 - 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-γ to protective immunity. In this study, we further characterized the role of Th1-type cytokines; IL-12, IFN-γ, and IFN-γ signaling using mice genetically deficient in IL-12, IFN-γ, or IFN-γ 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-γ resulted in correspondingly reduced IFN-γ or IL-12 production, respectively, suggesting an intricate interdependence in the induction of these cytokines. Collectively, these results suggest that the IL-12/ IFN-γ 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.
AB - 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-γ to protective immunity. In this study, we further characterized the role of Th1-type cytokines; IL-12, IFN-γ, and IFN-γ signaling using mice genetically deficient in IL-12, IFN-γ, or IFN-γ 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-γ resulted in correspondingly reduced IFN-γ or IL-12 production, respectively, suggesting an intricate interdependence in the induction of these cytokines. Collectively, these results suggest that the IL-12/ IFN-γ 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.
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U2 - 10.1089/jir.2009.0083
DO - 10.1089/jir.2009.0083
M3 - Article
C2 - 20187773
AN - SCOPUS:77953598952
SN - 1079-9907
VL - 30
SP - 407
EP - 415
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
IS - 6
ER -