Re-appraising the role of T-cell derived interferon gamma in restriction of Mycobacterium tuberculosis in the murine lung

Abstract

T cells producing interferon gamma (IFN{gamma}) have long been considered a stalwart for immune protection against Mycobacterium tuberculosis (Mtb), but their relative importance to pulmonary immunity has been challenged by murine studies which achieved protection by adoptively transferred Mtb-specific IFN{gamma}-/-T cells. Using IFN{gamma}-/- T cell chimeric mice and adoptive transfer of IFN{gamma}-/-T cells into TCR{beta}-/-{delta}-/-mice, we demonstrate that control of lung Mtb burden is in fact dependent on T cell-derived IFN{gamma}, and furthermore, mice selectively deficient in T cell-derived IFN{gamma} develop exacerbated disease compared to T cell-deficient controls despite equivalent lung bacterial burdens. Deficiency in T cell-derived IFN{gamma} skews infected and bystander monocyte-derived macrophages (MDMs) to an alternative M2 phenotype, and promotes neutrophil and eosinophil influx. Our studies support an important role for T cell-derived IFN{gamma} in pulmonary immunity against TB.