Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction
Abstract
Postviral bacterial infections are a major health care challenge in coronavirus infections, including COVID-19; however, the coronavirus-specific mechanisms of increased host susceptibility to secondary infections remain unknown. In humans, coronaviruses, including SARS-CoV-2, infect lung immune cells, including alveolar macrophages, a phenotype poorly replicated in mouse models of SARS-CoV-2. To overcome this, we used a mouse model of native murine β-coronavirus that infects both immune and structural cells to investigate coronavirus-enhanced susceptibility to bacterial infections. Our data show that coronavirus infection impairs the host ability to clear invading bacterial pathogens and potentiates lung tissue damage in mice. Mechanistically, coronavirus limits the bacterial killing ability of macrophages by impairing lysosomal acidification and fusion with engulfed bacteria. In addition, coronavirus-induced lysosomal dysfunction promotes pyroptotic cell death and the release of IL-1β. Inhibition of cathepsin B decreased cell death and IL-1β release and promoted bacterial clearance in mice with postcoronavirus bacterial infection.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 01, 2022
- Source ID
- 10.4049/jimmunol.2200198
Entities
People
- Asawari Korde
- Charles S Dela Cruz
- Craig B Wilen
- De Chang
- Gayatri Gupta
- Hyeon Jun Shin
- Jonathon P. Audia
- Jooyoung Kim
- Karen Agaronyan
- Lin Wang
- Lokesh Sharma
- Madeleine C Mankowski
- Min-Jong Kang
- Sarah Voth
- Shervin S. Takyar
- Shuta Ishibe
- Susan R Compton
- Victoria Habet
- Xiaohua Peng
- Xinran Liu
- Xuefei Tian
- Ying Cai
Organizations
- American Lung Association
- Chongqing Medical University
- United States Department of Defense
- United States Department of Veterans Affairs
- University of South Alabama
- Veterans Health Administration
- Yale School of Medicine
- Yale University