Determining the mechanistic basis for Irgm1 mediated control of <i>Mycobacterium tuberculosis</i>infection.

Abstract Irgm1 is a 47kDa IFN-γ inducible GTPase that has been shown to be essential for controlling Mycobacterium tuberculosis (Mtb) infection in mice. It was originally recruited Mtb containing phagosomes infected macrophages where it proposed involved autophagy-mediated clearance of Mtb. However, we have previously discovered autophagy not required control replication. In addition, since reported does colocalize with bovis BCG treated cells, suggesting must non-autophagic roles TB require detailed investigation. −/−mice were higher levels type I interferon signaling, as well CD4 +T cell survival defect, which could explain the susceptibility infection, but this yet determined. We Irgm1−/−mice and found they succumbed early bacterial burden, numbers neutrophils, CD19 +B lower +T-lymphocytes lungs compared wild-type (WT) significantly increased expression interferon-stimulated genes (ISGs) during WT. also observed T proliferation lymph node responses severely defective following Irgm1−/−mice. Bone marrow chimera transfer Mtb-specific activated lymphocytes into reverses indicating defect contributes infection. This work supported by Stephen I. Morse fellowship Sumanta Kumar Naik Project NIH AI142784 AI132697 BWF PATH Award Dr. Christina Stallings.