{"id":8511,"date":"2022-04-09T10:43:09","date_gmt":"2022-04-09T01:43:09","guid":{"rendered":"https:\/\/www.emukk.com\/WP\/?p=8511"},"modified":"2022-04-09T12:10:44","modified_gmt":"2022-04-09T03:10:44","slug":"cd169-siglec-1-facilitated-ace2-independent-sars-cov-2-fusion-and-entry-in-macrophages-and-induced-significant-expression-of-pro-inflammatory-cytokines","status":"publish","type":"post","link":"https:\/\/www.emukk.com\/WP\/en\/cd169-siglec-1-facilitated-ace2-independent-sars-cov-2-fusion-and-entry-in-macrophages-and-induced-significant-expression-of-pro-inflammatory-cytokines\/","title":{"rendered":"CD169\/Siglec-1 (I-type Lectin) facilitated ACE2-independent SARS-CoV-2 fusion and entry in macrophages"},"content":{"rendered":"<p>A group from Department of Microbiology, Boston University School of Medicine, Boston, MA, USA, etc. has reported <strong>CD169\/Siglec-1, a myeloid cell specific I-type lectin<\/strong>, facilitated ACE2-independent SARS-CoV-2 fusion and entry in macrophages.<br \/>\n<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/35378756\/\">https:\/\/pubmed.ncbi.nlm.nih.gov\/35378756\/<\/a><\/p>\n<p>Circulating monocytes, macrophages, and tissue-resident alveolar macrophages are not known to express ACE2, infection receptor of SARS-CoV-2. These cells have been shown to express low levels of TMPRSS2, and moderate levels of endosomal cathepsins which are necessary proteases for SARS-CoV-2 infection. CD169\/Siglec-1 (I-type lectin) is highly expressed by splenic red pulp and perifollicular macrophages, subcapsular sinus macrophages and alveolar macrophages. It is also known that CD169\/Siglec-1 expression can be upregulated on peripheral blood monocytes under inflammatory conditions, especially in response to type I interferons (IFNs).<\/p>\n<p>In this study, it was examined the mechanisms by which macrophages potentially contribute to inflammation during SARS-CoV-2 infection, using two different human macrophage models, PMA-differentiated THP1 cells (THP1\/PMA) and primary monocyte-derived macrophages (MDMs) expressing a myeloid cell-specific receptor, CD169\/Siglec-1, in the presence or absence of ACE2.<\/p>\n<p>Pre-treatment with antibodies targeting SARS-CoV-2 S NTD and inhibition of endosomal cathepsins by E64D markedly attenuated S-pseudotyped lentiviral infection in CD169<sup>+<\/sup> macrophages, but a TMPRSS2 inhibitor (Camostat) had no effect, suggesting that SARS-CoV-2 S facilitates <strong>endosomal viral entry<\/strong> into ACE2-deficient monocyte-derived macrophages (MDMs).<br \/>\nAlso, THP1 cells expressing CD169 displayed robust SARS-CoV-2 S binding comparable to levels observed with THP1\/ACE2 cells.<\/p>\n<p>Interestingly, CD169-expressing THP1\/PMA cells showed low levels of virus dsRNA production that did not significantly increase over the course of infection. However, significant expression of pro-inflammatory cytokines, IL-6, TNF\u03b1, IL-1\u03b2, and IL-18, was induced in infected CD169<sup>+<\/sup> THP1\/PMA macrophages compared to the parental THP1\/PMA cells, indicating that early viral RNA production is the key trigger of innate immune activation, in other words, SARS-CoV-2 infection of macrophages could induce pro-inflammatory responses finally resulting in cytokine storms.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>A group from Department of Microbiology, Boston University School of Medicine, Boston, MA, USA, etc. has repor<\/p><\/div>\n<div class=\"blog-btn\"><a href=\"https:\/\/www.emukk.com\/WP\/en\/cd169-siglec-1-facilitated-ace2-independent-sars-cov-2-fusion-and-entry-in-macrophages-and-induced-significant-expression-of-pro-inflammatory-cytokines\/\" class=\"home-blog-btn\">\u7d9a\u304d\u3092\u8aad\u3080<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[70],"tags":[],"class_list":["post-8511","post","type-post","status-publish","format-standard","hentry","category-nature-en"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/posts\/8511","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/comments?post=8511"}],"version-history":[{"count":7,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/posts\/8511\/revisions"}],"predecessor-version":[{"id":8529,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/posts\/8511\/revisions\/8529"}],"wp:attachment":[{"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/media?parent=8511"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/categories?post=8511"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.emukk.com\/WP\/wp-json\/wp\/v2\/tags?post=8511"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}