TY - JOUR
T1 - Contribution of interleukin-12 p35 (il-12p35) and il-12p40 to protective immunity and pathology in mice infected with chlamydia muridarum
AU - Chen, Lili
AU - Lei, Lei
AU - Zhou, Zhou
AU - He, Jie
AU - Xu, Sha
AU - Lu, Chunxue
AU - Chen, Jianlin
AU - Yang, Zhangsheng
AU - Wu, Gangqiu
AU - Yeh, I. Tien
AU - Zhong, Guangming
AU - Wu, Yimou
PY - 2013/8
Y1 - 2013/8
N2 - The p35 molecule is unique to interleukin-12 (IL-12), while p40 is shared by both IL-12 and IL-23. IL-12 promotes Th1 T cell responses, while IL-23 promotes Th17 T cell responses. The roles of IL-12p35-and IL-12p40-mediated responses in chlamydial infection were compared in mice following an intravaginal infection with Chlamydia muridarum. Mice deficient in either IL-12p35 or p40 both developed similar but prolonged infection time courses, confirming the roles of IL-12-mediated immune responses in clearing primary infection. However, all mice, regardless of genotype, cleared reinfection within 2 weeks, suggesting that an IL-12-or IL-23-independent adaptive immunity is protective against chlamydial infection. All infected mice developed severe oviduct hydrosalpinx despite the increased Th2 responses in IL-12p35-or IL-12p40-deficient mice, suggesting that Th2-dominant responses can contribute to Chlamydia-induced inflammatory pathology. Compared to IL-12p35 knockout mice, the IL-12p40-deficient mice exhibited more extensive spreading of chlamydial organisms into kidney tissues, leading to significantly increased incidence of pyelonephritis, which both confirms the role of IL-12 or IL-23-independent host responses in Chlamydia-induced pathologies and suggests that in the absence of IL-12/IFN-γ-mediated Th1 immunity, an IL-23-mediated response may play an important role in restricting chlamydial organisms from spreading into distal organs. These observations together provide important information for both understanding chlamydial pathogenesis and developing anti-Chlamydia vaccines.
AB - The p35 molecule is unique to interleukin-12 (IL-12), while p40 is shared by both IL-12 and IL-23. IL-12 promotes Th1 T cell responses, while IL-23 promotes Th17 T cell responses. The roles of IL-12p35-and IL-12p40-mediated responses in chlamydial infection were compared in mice following an intravaginal infection with Chlamydia muridarum. Mice deficient in either IL-12p35 or p40 both developed similar but prolonged infection time courses, confirming the roles of IL-12-mediated immune responses in clearing primary infection. However, all mice, regardless of genotype, cleared reinfection within 2 weeks, suggesting that an IL-12-or IL-23-independent adaptive immunity is protective against chlamydial infection. All infected mice developed severe oviduct hydrosalpinx despite the increased Th2 responses in IL-12p35-or IL-12p40-deficient mice, suggesting that Th2-dominant responses can contribute to Chlamydia-induced inflammatory pathology. Compared to IL-12p35 knockout mice, the IL-12p40-deficient mice exhibited more extensive spreading of chlamydial organisms into kidney tissues, leading to significantly increased incidence of pyelonephritis, which both confirms the role of IL-12 or IL-23-independent host responses in Chlamydia-induced pathologies and suggests that in the absence of IL-12/IFN-γ-mediated Th1 immunity, an IL-23-mediated response may play an important role in restricting chlamydial organisms from spreading into distal organs. These observations together provide important information for both understanding chlamydial pathogenesis and developing anti-Chlamydia vaccines.
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U2 - 10.1128/IAI.00161-13
DO - 10.1128/IAI.00161-13
M3 - Article
C2 - 23753624
AN - SCOPUS:84880647917
SN - 0019-9567
VL - 81
SP - 2962
EP - 2971
JO - Infection and immunity
JF - Infection and immunity
IS - 8
ER -