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Natural Killer T Cells Are Critical for Dendritic Cells to Induce Immunity in Chlamydial Pneumonia

¹ Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

Correspondence and requests for reprints should be addressed to Xi Yang, M.D., Ph.D., Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Room 523, 730 William Avenue, Winnipeg, MB, R3E 0W3 Canada. E-mail: yangxi{at}cc.umanitoba.ca

Rationale: We previously showed an important role of natural killer T cells (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.

Measurements and Main Results: We found that NKT activation in vivo after Cpn infection induces phenotypic and functional changes in dendritic cells (DC). DC from NKT-deficient mice showed reduced CD40 expression and IL-12 production, whereas enhancing NKT activation using -GalCer increased CD40 expression and IL-12 production. Co-culture of DC with NKT enhanced bioactive IL-12p70 production by DC in a CD40L-, IFN-–, and cell–cell contact–dependent manner. Further, co-culture of T cells with DC isolated from infected wild-type (WT) and NKT-deficient mice induced type-1 and type-2 responses, respectively, while DC from -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 knockout mice induced type-2 responses and increased disease severity upon challenge infection.

Conclusions: Our results provide direct evidence of the critical role of NKT activation in the functional modulation of DC for the development of protective immunity in a clinically relevant respiratory infection.

Key Words: NKT cells • dendritic cells • infection • Chlamydia • host defense

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Most previous studies on natural killer T cell (NKT)–dendritic cell (DC) interaction focused on the effect of DC on NKT. Limited knowledge on the role of NKT on DC function is from studies using -GalCer, a model lipid antigen. What This Study Adds to the Field We show a critical role of NKT in modulating DC function and the type of adaptive T cell responses in a clinically relevant bacterial pneumonia model.