Re-appraising the role of T-cell derived interferon gamma in restriction ofMycobacterium tuberculosisin the murine lung

Abstract

ABSTRACTT cells producing interferon gamma (IFNγ) have long been considered a stalwart for immune protection againstMycobacterium tuberculosis(Mtb), but their relative importance to pulmonary immunity has been challenged by murine studies which achieved protection by adoptively transferredMtb-specific IFNγ-/-T cells. Using IFNγ-/-T cell chimeric mice and adoptive transfer of IFNγ-/-T cells into TCRβ-/-δ-/-mice, we demonstrate that control of lungMtbburden is in fact dependent on T cell-derived IFNγ, and furthermore, mice selectively deficient in T cell-derived IFNγ develop exacerbated disease compared to T cell-deficient controls despite equivalent lung bacterial burdens. Deficiency in T cell-derived IFNγ 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 IFNγ in pulmonary immunity against TB.