Natural killer T cells are critical for dendritic cells to induce immunity in Chlamydial pneumonia.
BACKGROUND
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.


OBJECTIVE
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.


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 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-, IFN-gamma-, 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 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 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.
Joyee
Antony George
AG
Laboratory for Infection and Immunity, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
Qiu
Hongyu
H
Fan
Yijun
Y
Wang
Shuhe
S
Yang
Xi
X
D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002690:Chlamydia Infections / Q000276:immunology*; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000276:immunology*
D016207:Cytokines