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Nat. Commun., Published: 07 June 2022 | https://doi.org/10.1038/s41467-022-30914-3 Viral coinfection promotes tuberculosis immunopathogenesis by type I IFN signaling-dependent impediment of Th1 cell pulmonary influx

Tae Gun Kang^1,2,7, Kee Woong Kwon^3,7, Kyungsoo Kim^1,4, Insuk Lee⁵, Myeong Joon Kim^1,2, Sang-Jun Ha^1,2,* & Sung Jae Shin^3,6,*

¹Department of Biochemistry, College of Life Science & Biotechnology, Yonsei University, Seoul 03722, Republic of Korea. ²Brain Korea 21 (BK21) FOUR Program, Yonsei Education & Research Center for Biosystems, Yonsei University, Seoul 03722, Republic of Korea. ³Department of Microbiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. ⁴Institute for Breast Cancer Precision Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. ⁵Department of Biotechnology, College of Life Science & Biotechnology, Yonsei University, Seoul 03722, Republic of Korea. ⁶Institute for Immunology and Immunological Disease, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. ⁷These authors contributed equally: Tae Gun Kang, Kee Woong Kwon.

^*Corresponding author.

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.

논문정보

형식Research article
게재일2022년 06월 (BRIC 등록일 2022-06-27)
연구진국내 연구진
분야 생명과학 > 면역학

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