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

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 significant...

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Published in:Nature communications 2022-06, Vol.13 (1), p.3155-3155, Article 3155
Main Authors: Kang, Tae Gun, Kwon, Kee Woong, Kim, Kyungsoo, Lee, Insuk, Kim, Myeong Joon, Ha, Sang-Jun, Shin, Sung Jae
Format: Article
Language:English
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Summary: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 cells. Thus, our study suggests that augmented and sustained type I IFNs by virus coinfection prior to the pulmonary localization of Mtb-specific Th1 cells exacerbates TB immunopathogenesis by impeding the Mtb-specific Th1 cell influx. Our study highlights a negative function of viral coinfection-induced type I IFN responses in delaying Mtb-specific Th1 responses in the lung. Viral coinfection alongside mycobacterium tuberculosis (Mtb) infection may lead to immune complications or interference with immune responses. Here the authors show that in mice infected with Mtb and LCMV virus the specific T H 1 response to MTb is reduced through a type I IFN response to the infecting virus.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-022-30914-3