Tweet
J Immunol
. 2022 Sep 2;ji2200198.
doi: 10.4049/jimmunol.2200198. Online ahead of print.
Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction
Xiaohua Peng 1 2 , Jooyoung Kim 2 , Gayatri Gupta 2 , Karen Agaronyan 3 , Madeleine C Mankowski 4 , Asawari Korde 2 , Shervin S Takyar 2 , Hyeon Jun Shin 2 , Victoria Habet 5 , Sarah Voth 2 , Jonathon P Audia 6 , De Chang 2 7 , Xinran Liu 8 9 , Lin Wang 2 10 , Ying Cai 2 , Xuefei Tian 11 , Shuta Ishibe 11 , Min-Jong Kang 2 , Susan Compton 12 , Craig B Wilen 5 13 , Charles S Dela Cruz 14 15 16 , Lokesh Sharma 14
Affiliations
- PMID: 36165196
- DOI: 10.4049/jimmunol.2200198
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.