S.Seneff
Member
- Joined
- Mar 18, 2020
- Messages
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https://www.medrxiv.org/content/10.1101/2020.03.27.20045427v1.full.pdf
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.
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.