Journal article
Coronavirus-specific antibody production in middle-aged mice requires phospholipase A2G2D
The Journal of clinical investigation, Vol.131(11), e147201
06/01/2021
DOI: 10.1172/JCI147201
PMCID: PMC8266207
PMID: 34060490
Abstract
Worse outcomes occur in aged compared with young populations after infections with respiratory viruses, including pathogenic coronaviruses (SARS-CoV, MERS-CoV, and SARS-CoV-2), and are associated with a suboptimal lung milieu (“inflammaging”). We previously showed that a single inducible phospholipase, PLA2G2D, is associated with a proresolving/antiinflammatory response in the lungs, and increases with age. Survival was increased in naive Pla2g2d–/– mice infected with SARS-CoV resulting from augmented respiratory dendritic cell (rDC) activation and enhanced priming of virus-specific T cells. Here, in contrast, we show that intranasal immunization provided no additional protection in middle-aged Pla2g2d–/– mice infected with any of the 3 pathogenic human coronaviruses because virtually no virus-specific antibodies or follicular helper CD4+ T (Tfh) cells were produced. Using MERS-CoV–infected mice, we found that these effects did not result from T or B cell intrinsic factors. Rather, they resulted from enhanced, and ultimately, pathogenic rDC activation, as manifested most prominently by enhanced IL-1β expression. Wild-type rDC transfer to Pla2g2d–/– mice in conjunction with partial IL-1β blockade reversed this defect and resulted in increased virus-specific antibody and Tfh responses. Together, these results indicate that PLA2G2D has an unexpected role in the lungs, serving as an important modulator of rDC activation, with protective and pathogenic effects in respiratory coronavirus infections and immunization, respectively.
Details
- Title: Subtitle
- Coronavirus-specific antibody production in middle-aged mice requires phospholipase A2G2D
- Creators
- Jian ZhengDavid MeyerholzLok-Yin Roy WongMichael GelbMakoto MurakamiStanley Perlman
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.131(11), e147201
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI147201
- PMID
- 34060490
- PMCID
- PMC8266207
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Grant note
- name: N.I.H., USA, award: RO1 AI129269, PO1 AI060699
- Language
- English
- Date published
- 06/01/2021
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984084133302771
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