{"id":36919,"date":"2025-07-04T12:51:06","date_gmt":"2025-07-04T10:51:06","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/07\/04\/borrelia-burgdorferi-c-di-amp-is-a-key-extracellular-pathogen-associated-molecular-pattern-to-elicit-type-i-interferon-responses-in-mammalian-hosts\/"},"modified":"2025-07-04T12:51:06","modified_gmt":"2025-07-04T10:51:06","slug":"borrelia-burgdorferi-c-di-amp-is-a-key-extracellular-pathogen-associated-molecular-pattern-to-elicit-type-i-interferon-responses-in-mammalian-hosts","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/07\/04\/borrelia-burgdorferi-c-di-amp-is-a-key-extracellular-pathogen-associated-molecular-pattern-to-elicit-type-i-interferon-responses-in-mammalian-hosts\/","title":{"rendered":"Borrelia burgdorferi c-di-AMP is a key extracellular pathogen-associated molecular pattern to elicit type I interferon responses in mammalian hosts"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2025 Jul 3:vkaf133. doi: 10.1093\/jimmun\/vkaf133. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Borrelia burgdorferi (or Borreliella burgdorferi), the extracellular spirochete responsible for Lyme disease, elicits a type I interferon (IFN-I) response critical for the development of Lyme arthritis. However, the specific pathogen-associated molecular pattern (PAMP) driving this response remains unidentified. Previous studies have reported that B. burgdorferi culture supernatants significantly stimulate macrophage IFN-I responses, but the responsible component was unknown. In this study, we identified cyclic-di-adenosine monophosphate (c-di-AMP) as the critical PAMP for the induction of IFN response. Inactivation of cdaA, which encodes diadenylate cyclase for c-di-AMP synthesis, significantly reduced IFN-\u03b2 production in murine macrophage cell lines (RAW264.7) and bone marrow-derived macrophages. Conversely, the deletion of dhhP, which encodes c-di-AMP phosphodiesterase, dramatically increased IFN-\u03b2 production. We further demonstrated that B. burgdorferi releases c-di-AMP, which is the major component in the culture supernatant responsible for stimulating the IFN-I response in macrophages. Furthermore, B. burgdorferi c-di-AMP-induced IFN-I response depends on STING, as inactivation or inhibition of STING signaling markedly reduced IFN-I induction. These findings establish c-di-AMP as a key PAMP of B. burgdorferi that activates host STING signaling to induce IFN-I responses, highlighting its potential as a therapeutic target for Lyme arthritis.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/40611506\/?utm_source=WordPress&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20250704065103&amp;v=2.18.0.post9+e462414\">40611506<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf133\">10.1093\/jimmun\/vkaf133<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2025 Jul 3:vkaf133. doi: 10.1093\/jimmun\/vkaf133. Online ahead of print. ABSTRACT Borrelia burgdorferi (or Borreliella burgdorferi), the extracellular spirochete responsible for Lyme disease, elicits a type I interferon (IFN-I) response critical for the development of Lyme arthritis. However, the specific pathogen-associated molecular pattern (PAMP) driving this response remains unidentified. Previous studies have reported that &#8230; <a title=\"Borrelia burgdorferi c-di-AMP is a key extracellular pathogen-associated molecular pattern to elicit type I interferon responses in mammalian hosts\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/07\/04\/borrelia-burgdorferi-c-di-amp-is-a-key-extracellular-pathogen-associated-molecular-pattern-to-elicit-type-i-interferon-responses-in-mammalian-hosts\/\" aria-label=\"Read more about Borrelia burgdorferi c-di-AMP is a key extracellular pathogen-associated molecular pattern to elicit type I interferon responses in mammalian hosts\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-36919","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/36919","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"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=36919"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/36919\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=36919"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=36919"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=36919"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}