Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction.
J Immunol
; 209(7): 1314-1322, 2022 10 01.
Article
in English
| MEDLINE | ID: covidwho-2055633
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 ß-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-1ß. Inhibition of cathepsin B decreased cell death and IL-1ß release and promoted bacterial clearance in mice with postcoronavirus bacterial infection.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Bacterial Infections
/
Murine hepatitis virus
/
Coinfection
/
COVID-19
Limits:
Animals
/
Humans
Language:
English
Journal:
J Immunol
Year:
2022
Document Type:
Article
Affiliation country:
Jimmunol.2200198
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