Nkt Cells Prevent Chronic Joint Inflammation After Infection With Borrelia Burgdorferi

摘要

Borrelia burgdorferi is the etiologic agent of Lyme disease, a multisystem inflammatory disorder that principally targets the skin, joints, heart, and nervous system. The role of T lymphocytes in the development of chronic inflammation resulting from B. burgdorferi infection has been controversial. We previously showed that natural killer T (NKT) cells with an invariant (i) TCR α chain (iNKT cells) recognize glycolipids from B. burgdorferi, but did not establish an in vivo role for iNKT cells in Lyme disease patho-genesis. Here, we evaluate the importance of iNKT cells for host defense against these pathogenic spirochetes by using Vα14i NKT cell-deficient (Jα18~(-/-)) BALB/c mice. On tick inoculation with B. burgdorferi, Jα18~(-/-) mice exhibited more severe and prolonged arthritis as well as a reduced ability to clear spirochetes from infected tissues. Vα14/NKT cell deficiency also resulted in increased production of antibodies directed against both B. burgdorferi protein antigens and borrelial diacylglycerols; the latter finding demonstrates that anti-glycolipid antibody production does not require cognate help from Vα14i NKT cells. Vα14i NKT cells in infected wild-type mice expressed surface activation markers and produced IFN-γ in vivo after infection, suggesting a participatory role for this unique population in cellular immunity. Our data are consistent with the hypothesis that the antigen-specific activation of Vα14i NKT cells is important for the prevention of persistent joint inflammation and spirochete clearance, and they counter the long-standing notion that humoral rather than cellular immunity is sufficient to facilitate Lyme disease resolution.