68 171

Cited 2 times in

Murine Coronavirus Disease 2019 Lethality Is Characterized by Lymphoid Depletion Associated with Suppressed Antigen-Presenting Cell Functionality

Authors
 Yu Jin Lee  ;  Sang Hyeok Seok  ;  Na Yun Lee  ;  Hee Jin Choi  ;  Yoon Woo Lee  ;  Hee Jung Chang  ;  Ji-Yeon Hwang  ;  Da In On  ;  Hyun Ah Noh  ;  Su-Bin Lee  ;  Ho-Keun Kwon  ;  Jun-Won Yun  ;  Jeon-Soo Shin  ;  Jun-Young Seo  ;  Ki Taek Nam  ;  Ho Lee  ;  Ho Young Lee  ;  Jun Won Park  ;  Je Kyung Seong 
Citation
 AMERICAN JOURNAL OF PATHOLOGY, Vol.193(7) : 866-882, 2023-07 
Journal Title
AMERICAN JOURNAL OF PATHOLOGY
ISSN
 0002-9440 
Issue Date
2023-07
MeSH
Animals ; Antigen-Presenting Cells ; COVID-19* ; Disease Models, Animal ; Disease Susceptibility ; Humans ; Lung / metabolism ; Mice ; Mice, Transgenic ; Peptidyl-Dipeptidase A / metabolism ; SARS-CoV-2 / metabolism
Abstract
The disease severity of coronavirus disease 2019 (COVID-19) varies considerably from asymptomatic to serious, with fatal complications associated with dysregulation of innate and adaptive immunity. Lymphoid depletion in lymphoid tissues and lymphocytopenia have both been associated with poor disease outcomes in patients with COVID-19, but the mechanisms involved remain elusive. In this study, human angiotensin-converting enzyme 2 (hACE2) transgenic mouse models susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were used to investigate the characteristics and determinants of lethality associated with the lymphoid depletion observed in SARS-CoV-2 infection. The lethality of Wuhan SARS-CoV-2 infection in K18-hACE2 mice was characterized by severe lymphoid depletion and apoptosis in lymphoid tissues related to fatal neuroinvasion. The lymphoid depletion was associated with a decreased number of antigen-presenting cells (APCs) and their suppressed functionality below basal levels. Lymphoid depletion with reduced APC function was a specific feature observed in SARS-CoV-2 infection but not in influenza A infection and had the greatest prognostic value for disease severity in murine COVID-19. Comparison of transgenic mouse models resistant and susceptible to SARS-CoV-2 infection revealed that suppressed APC function could be determined by the hACE2 expression pattern and interferon-related signaling. Thus, we demonstrated that lymphoid depletion associated with suppressed APC function characterizes the lethality of COVID-19 mouse models. Our data also suggest a potential therapeutic approach to prevent the severe progression of COVID-19 by enhancing APC functionality. © 2023 American Society for Investigative Pathology
Files in This Item:
T202304172.pdf Download
DOI
10.1016/j.ajpath.2023.03.008
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kwon, Ho-Keun(권호근) ORCID logo https://orcid.org/0000-0003-3175-0376
Nam, Ki Taek(남기택)
Seo, Jun Young(서준영) ORCID logo https://orcid.org/0000-0003-4004-2013
Shin, Jeon Soo(신전수) ORCID logo https://orcid.org/0000-0002-8294-3234
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/195973
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links