Activation of NKT Cells Protects Mice from Tuberculosis

Abstract

ABSTRACT The T-cell immune response to Mycobacterium tuberculosis is critical in preventing clinical disease. While it is generally accepted that both major histocompatibility complex class I (MHC-I)-restricted CD8 + and MHC-II-restricted CD4 + T cells are important for the immune response to M. tuberculosis , the role of non-MHC-restricted T cells is still not clearly delineated. We have previously reported that CD1d −/− mice do not differ from CD1d +/+ mice in their survival following infection with M. tuberculosis . We now show that, although CD1d-restricted NKT cells are not required for optimum immunity to M. tuberculosis , specific activation of NKT cells by the CD1d ligand α-galactosylceramide protects susceptible mice from tuberculosis. Treatment with α-galactosylceramide reduced the bacterial burden in the lungs, diminished tissue injury, and prolonged survival of mice following inoculation with virulent M. tuberculosis . The capacity of activated NKT cells to stimulate innate immunity and modulate the adaptive immune response to promote a potent antimicrobial immune response suggests that α-galactosylceramide administration could have a role in new strategies for the therapy of infectious diseases.