VEGFR1 blockade reduces <i>Mycobacterium tuberculosis</i>-induced pathology in immunocompromised mice

Abstract Mycobacterium tuberculosis (Mtb) is a major public health concern that caused 1.6 million deaths in 2021. New treatments are needed, especially immunocompromised individuals, such as patients with HIV coinfection, who severely impacted by the disease. We have recently reported blocking VEGFR1, receptor present on monocytes and contributes to their recruitment sites of infection, limits Mtb-induced pathology immunocompetent mice both Mtb-resistant (C57BL/6J) Mtb-supersusceptible (C3HeB/FeJ) strains (Harding et al., 2019). These results offer way reduce lung without impeding host defense. Here, we extend this finding showing VEGFR1 blockade has similar effects (RAG1KO) well, measured reduction area inflammation change bacterial burden. Following treatment blocker SU5416, found an elevated ratio increase absolute number neutrophil granulocytes Mtb-infected lungs immunosufficient mice. Surprisingly however, did not result exacerbated majority recruited neutrophils remained vasculature. Our indicate further evaluation blockers adjunctive antitubercular drug therapy for populations could be worthwhile. Supported grants from NIH (R01 HL128778 R01 NS123449)