Viral coinfection promotes tuberculosis immunopathogenesis by type I IFN signaling-dependent impediment of Th1 cell pulmonary influx.

ABSTRACT: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is often exacerbated upon coinfection, but the underlying immunological mechanisms remain unclear. Here, to elucidate these mechanisms, we use an Mtb and lymphocytic choriomeningitis virus coinfection model. Viral coinfection significantly suppresses Mtb-specific IFN-γ production, with elevated bacterial loads and hyperinflammation in the lungs. Type I IFN signaling blockade rescues the Mtb-specific IFN-γ response and ameliorates lung immunopathology. Single-cell sequencing, tissue immunofluorescence staining, and adoptive transfer experiments indicate that viral infection-induced type I IFN signaling could inhibit CXCL9/10 production in myeloid cells, ultimately impairing pulmonary migration of Mtb-specific CD4⁺ T c

SUBMITTER: Kang TG 

PROVIDER: S-EPMC9174268 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature