{"id":25367,"date":"2025-02-21T07:02:20","date_gmt":"2025-02-21T06:02:20","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/02\/21\/il-6-mediates-defense-against-influenza-virus-by-promoting-protective-antibody-responses-but-not-innate-inflammation-f-piattini\/"},"modified":"2025-02-21T07:02:20","modified_gmt":"2025-02-21T06:02:20","slug":"il-6-mediates-defense-against-influenza-virus-by-promoting-protective-antibody-responses-but-not-innate-inflammation-f-piattini","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/02\/21\/il-6-mediates-defense-against-influenza-virus-by-promoting-protective-antibody-responses-but-not-innate-inflammation-f-piattini\/","title":{"rendered":"IL-6 mediates defense against influenza virus by promoting protective antibody responses but not innate inflammation. F Piattini"},"content":{"rendered":"<div>\n<p><b>Mucosal Immunol<\/b>. 2025 Feb 18:S1933-0219(25)00019-4. doi: 10.1016\/j.mucimm.2025.02.001. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Influenza virus infection is a leading cause of morbidity and mortality worldwide, posing a significant public health problem. The pro-inflammatory cytokine interleukin-6 (IL-6) has been shown to promote defense against respiratory viral infection, while excessive IL-6 responses have been associated with severe pneumonia. Heterogenous expression of IL-6R and the IL-6-signal transducer subunit (gp130) across many cell types and different signaling modalities have made it difficult to define the precise role of the IL-6\/IL-6R pathway in vivo. We generated multiple cell lineage-specific Il6ra-deficient mice and compared them to global Il6ra<sup>-\/-<\/sup> and Il-6<sup>-\/-<\/sup> mice to dissect the systemic and cell-intrinsic mechanisms for pneumonitis and control of influenza A virus (IAV) infection. Delayed viral clearance and severe morbidity in the global IL-6 knockouts were associated with reduced antibody responses, complement C3 and C5 production, and impaired T follicular helper (Tfh) cell generation. Mice lacking IL-6R exclusively in T cells phenocopied a defect in Tfh cell differentiation and antibody production, although susceptibility to IAV was only mildly affected. Mice lacking IL-6R specifically in B cells mounted normal antibody responses. Moreover, innate pro-inflammatory cytokine responses, myeloid cell infiltration, and adaptive immunity in the lung remained unaffected in Il6ra<sup>fl\/fl<\/sup>LysM<sup>Cr<\/sup><sup>e<\/sup> mice. Our results suggest that IL-6 mediates defense against IAV mainly by generating Tfh cells and promoting local C3 production, which together are required for eliciting protective antibody responses by B cells.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39978550\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20250221010219&amp;v=2.18.0.post9+e462414\">39978550<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2025.02.001\">10.1016\/j.mucimm.2025.02.001<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2025 Feb 18:S1933-0219(25)00019-4. doi: 10.1016\/j.mucimm.2025.02.001. Online ahead of print. ABSTRACT Influenza virus infection is a leading cause of morbidity and mortality worldwide, posing a significant public health problem. The pro-inflammatory cytokine interleukin-6 (IL-6) has been shown to promote defense against respiratory viral infection, while excessive IL-6 responses have been associated with severe pneumonia. &#8230; <a title=\"IL-6 mediates defense against influenza virus by promoting protective antibody responses but not innate inflammation. F Piattini\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/02\/21\/il-6-mediates-defense-against-influenza-virus-by-promoting-protective-antibody-responses-but-not-innate-inflammation-f-piattini\/\" aria-label=\"Read more about IL-6 mediates defense against influenza virus by promoting protective antibody responses but not innate inflammation. F Piattini\">Read more<\/a><\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[57,42],"tags":[],"class_list":["post-25367","post","type-post","status-publish","format-standard","hentry","category-mucosal-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/25367","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=25367"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/25367\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=25367"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=25367"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=25367"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}