Mice infected with Mycobacterium tuberculosis are resistant to secondary infection with SARS-CoV-2

Abstract

Abstract Mycobacterium tuberculosis (Mtb)and SARS-CoV-2 (CoV2) are the leading causes of death due to infectious disease; however, little is known regarding the immunological environment in the Mtb/CoV2 coinfected lung. The goal of this study was to use a mouse model of Mtb/CoV2 coinfection to determine if CoV2 affects Mtb bacterial burden and/or alters the lung immune profile. Using lung collected from human ACE2 transgenic (K18-hACE2) mice infected with both pathogens (Mtb only, SARS-CoV-2 only, and Mtb/SARS-CoV-2 co-infected), we evaluated immune gene expression, cytokine production, and bacterial burden. Surprisingly, these data show that Mtb suppresses CoV2 -related weight loss and lung viral burden in the human ACE2 transgenic mouse model. We also report a reduction in lung interferon gamma production and expression in coinfected mice compared to the Mtb only infected group, suggesting a possible altered T cell profile in the coinfected group. To determine whether Mtb-induced resistance to CoV2 was specific to the ACE2 transgenic model of COVID19, we performed the same set of experiments using a second mouse model of COVID19: Mouse Adapted SARS-CoV-2 (MACoV2) infection of C57BL/6 (B6) mice. In both model systems, Mtb-infected mice were resistant to secondary CoV2 infection and its pathological consequences, and CoV2 infection did not affect Mtb burdens. Single cell RNA sequencing of coinfected and monoinfected lungs demonstrated the resistance of Mtb-infected mice is associated with expansion of T and B cell subsets upon viral challenge. Collectively, these data demonstrate that Mtb infection conditions the lung environment in a manner that is not conducive to CoV2 survival. Supported by OSU Advancing Research in Infection and Immunity Fellowship Award