Type I IFNs exacerbate tuberculosis pathogenesis by inhibiting migration of antigen specific T cells

Tuberculosis, a chronic granulomatous disease caused by Mycobacterium tuberculosis (Mtb), often becomes exacerbated upon co-infection with other pathogens, yet the underlying immunological mechanisms remain insufficiently understood. Here, mice were initially infected with the hypervirulent Mtb strain K, and later with lymphocytic choriomeningitis virus to investigate the mechanism of severe pulmonary pathology. Virus infection significantly reduced Mtb-specific IFN-g, increased bacterial loads, and aggravated lung inflammation in the lung of Mtb-infected mice, which did not occur in pre-existence of Th1 response by Bacillus Calmette-Guerin vaccination prior to the co-infection. Blockade of type I IFN receptor signaling reinvigorated Mtb-specific IFN-γ response and ameliorated pathogenesis by upregulating pulmonary CXCL9/10 production. Our results demonstrate that virus-induced type I IFN triggers severe immunopathology by deteriorating migration of Mtb-specific IFN-γ-producing T cells, suggesting the balance between type I and type II IFNs determines either control of Mtb or exacerbation of pathology in the lung upon viral infection mRNA profile of Lung infitrating CD45+ immune cells from Naïve, Mtb only infected, Mtb+LCMV co-infected, Mtb+LCMV+aIFNAR1 co-infected mice at 21 days post Mtb infection