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The Novel Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) Directly Decimates Human Spleens and Lymph Nodes
yongwen chen; Zeqing Feng; Bo Diao; Rongshuai Wang; Gang Wang; Chenhui Wang; Yingjun Tan; Liang Liu; Changsong Wang; Ying Liu; Yueping Liu; Zilin Yuan; Liang Ren; Yuzhang Wu.
Afiliação
  • yongwen chen; Institute of Immunology, PLA, Third Military Medical University, Chongqing, China
  • Zeqing Feng; Institute of Immunology, PLA, Third Military Medical University, Chongqing, China
  • Bo Diao; Department of Medical Laboratory Center, General Hospital of Central Theater Command, Wuhan, China
  • Rongshuai Wang; Hubei Chongxin Judicial Expertise Center, Wuhan, China
  • Gang Wang; Institute of Immunology, PLA, Third Military Medical University, Chongqing, China
  • Chenhui Wang; Institute of Immunology, PLA, Third Military Medical University, Chongqing, China
  • Yingjun Tan; Department of Medical Laboratory Center, General Hospital of Central Theater Command, Wuhan, China
  • Liang Liu; Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan, China
  • Changsong Wang; Department of Pathology, 989th Hospital of PLA, Luoyang, China
  • Ying Liu; Department of Medical Laboratory Center, General Hospital of Central Theater Command, Wuhan, China
  • Yueping Liu; Department of Medical Laboratory Center, General Hospital of Central Theater Command, Wuhan, China
  • Zilin Yuan; Department of Medical Laboratory Center, General Hospital of Central Theater Command, Wuhan, China
  • Liang Ren; Hubei Chongxin Judicial Expertise Center, Wuhan, China
  • Yuzhang Wu; Institute of Immunology, PLA, Third Military Medical University, Chongqing, China
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20045427
ABSTRACT
While lymphocytopenia is a common characteristic of patients infected by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the mechanisms responsible for this depletion are unclear. Through careful inspection of the spleens and lymph nodes (LNs) from six cases with postmortem examinations, we observed that SARS-CoV-2 could directly infect secondary lymphoid organs to induce cell death. Immunohistochemistry demonstrated ACE2 (angiotensin-converting enzyme 2), the potential receptor of SARS-CoV-2, expresses on tissue-resident CD169+ macrophages in spleens and LNs. Immunofluorescent staining confirmed that viral nucleocaspid protein (NP) can be found in ACE2+ cells, CD169+ macrophages, but not in CD3+ T cells or B220+ B cells in spleens and LNs. SARS-CoV-2 infection induces severe tissue damage including lymph follicle depletion, splenic nodule atrophy, histiocyte hyperplasia and lymphocyte reductions. Moreover, in situ TUNEL staining illustrated that viral infection leads to severe lymphocyte apoptosis, which might be mediated by viral antigens inducing Fas upregulation. Furthermore, SARS-CoV-2 also triggers macrophages to produce IL-6, a proinflammatory cytokine that directly promotes lymphocyte necrosis. Collectively, these results demonstrate that SARS-CoV-2 directly neutralizes human spleens and LNs through infecting tissue-resident CD169+ macrophages.
Licença
cc_by_nc_nd
Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: medRxiv Idioma: Inglês Ano de publicação: 2020 Tipo de documento: Preprint
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