title: Invariant Natural Killer T Cells Promote T Cell Immunity by Modulating the Function of Lung Dendritic Cells during Chlamydia pneumoniae Infection.
abstract: In this study, we examined the effect of invariant natural killer T (iNKT) cells on the function of lung dendritic cells (LDCs) in eliciting protective immunity against Chlamydia pneumoniae (Cpn) lung infection. We employed a combination of approaches including the use of iNKT cell-deficient, Jα18-knockout (KO) mice and LDC adoptive transfer. We found that iNKT cells significantly altered the number, phenotype and cytokine profile of LDCs following infection. Furthermore, coculture of T cells with LDCs from Cpn-infected wild-type (WT) and KO mice induced type-1 and type-2 responses, respectively. More importantly, upon adoptive transfer, LDCs from Cpn-infected WT mice (WT-LDCs) conferred protective immunity, whereas LDCs from KO mice (KO-LDCs) increased the severity of disease after challenge infection. Further cytokine analyses of the lung tissues and lung-draining lymph node cells showed that KO-LDC-recipient mice exhibited a type-2 cytokine production pattern, while WT-LDC recipients exhibited a type-1 cytokine profile. Taken together, our results provide in vivo evidence that iNKT cells play a critical role in modulating LDC function to generate protective T-cell immunity, particularly in a clinically relevant intracellular bacterial infection.
authors.affiliation: Laboratory for Infection and Immunity, Department of Medical Microbiology, University of Manitoba, Winnipeg, Man., Canada.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Shekhar
authors.forename: Antony George
authors.initials: AG
authors.lastname: Joyee
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Shuhe
authors.initials: S
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D023521:Chlamydophila Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D007111:Immunity, Cellular; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology* / Q000473:pathology