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

ABSTRACT T cells producing interferon gamma (IFNγ) 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 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 lung Mtb burden 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.