Joyee AG, Qiu H, Fan Y, Wang S, Yang X
Natural Killer T Cells are Critical for Dendritic Cells to Induce Immunity in Chlamydial Pneumonia. [JOURNAL ARTICLE]
Am J Respir Crit Care Med 2008 Jul 2.
RATIONALE: We previously showed an important role of NKT in skewing the adaptive T cell immunity to Chlamydia pneumoniae (Cpn), an intracellular bacterial lung infection, but the mechanism remains unclear.
OBJECTIVES: To investigate the underlying mechanism by which NKT modulate T cell responses in chlamydial pneumonia.
METHODS: We examined the effect of NKT activation in modulating DC function especially in generating protective immunity against Cpn infection using combination of NKT knockout (KO) mice and specific NKT activation approaches.
MAIN RESULTS: We found that NKT activation in vivo following Cpn infection induces phenotypic and functional changes in DC. DC from NKT deficient mice showed reduced CD40 expression and IL-12 production, whereas enhancing NKT activation using alpha-GalCer increased CD40 expression and IL-12 production. Co-culture of DC with NKT enhanced bioactive IL-12p70 production by DC in a CD40L, IFNgammaand cell-cell contact dependent manner. Further, co-culture of T cells with DC isolated from infected WT and NKT deficient mice induced type-1 and type-2 responses, respectively, while DC from alpha-GalCer treated, infected mice led to enhanced type-1 responses. Moreover, upon adoptive transfer, DC from infected WT mice induced strong type-1 immunity whereas those from KO mice induced type-2 responses and increased disease severity upon challenge infection.
CONCLUSION: Our results provide direct evidence on the critical role of NKT activation in the functional modulation of DC for the development of protective immunity in a clinically relevant respiratory infection.
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