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

Author

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  • Tae Gun Kang

    (Yonsei University
    Brain Korea 21 (BK21) FOUR Program, Yonsei Education & Research Center for Biosystems, Yonsei University)

  • Kee Woong Kwon

    (Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine)

  • Kyungsoo Kim

    (Yonsei University
    Institute for Breast Cancer Precision Medicine, Yonsei University College of Medicine)

  • Insuk Lee

    (Yonsei University)

  • Myeong Joon Kim

    (Yonsei University
    Brain Korea 21 (BK21) FOUR Program, Yonsei Education & Research Center for Biosystems, Yonsei University)

  • Sang-Jun Ha

    (Yonsei University
    Brain Korea 21 (BK21) FOUR Program, Yonsei Education & Research Center for Biosystems, Yonsei University)

  • Sung Jae Shin

    (Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine
    Institute for Immunology and Immunological Disease, Yonsei University College of Medicine)

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 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.

Suggested Citation

  • Tae Gun Kang & Kee Woong Kwon & Kyungsoo Kim & Insuk Lee & Myeong Joon Kim & Sang-Jun Ha & Sung Jae Shin, 2022. "Viral coinfection promotes tuberculosis immunopathogenesis by type I IFN signaling-dependent impediment of Th1 cell pulmonary influx," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30914-3
    DOI: 10.1038/s41467-022-30914-3
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    References listed on IDEAS

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