.png){kind=icon}
.png){kind=icon}
Return
Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction
.png){kind=icon}
OA
AI
DOI：10.4049/jimmunol.2200198.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
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 13-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-113. Inhibition of cathepsin B decreased cell death and IL-113 release and promoted bacterial clearance in mice with postcoronavirus bacterial infection. The Journal of Immunology, 2022, 209: 1314-1322.
Keywords:
CLINICAL CHARACTERISTICS
CELL-DEATH
PYROPTOSIS
PNEUMONIA
CATHEPSINS
Journal
IF:
3.4
Papers:
3.7W
Citations:
9.9W
View more organizations