{"id":28102,"date":"2025-03-26T00:03:08","date_gmt":"2025-03-25T23:03:08","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/03\/26\/porphyromonas-gingivalis-outer-membrane-vesicles-divert-host-innate-immunity-and-promote-inflammation-via-c4-monophosphorylated-lipid-a\/"},"modified":"2025-03-26T00:03:08","modified_gmt":"2025-03-25T23:03:08","slug":"porphyromonas-gingivalis-outer-membrane-vesicles-divert-host-innate-immunity-and-promote-inflammation-via-c4-monophosphorylated-lipid-a","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/03\/26\/porphyromonas-gingivalis-outer-membrane-vesicles-divert-host-innate-immunity-and-promote-inflammation-via-c4-monophosphorylated-lipid-a\/","title":{"rendered":"Porphyromonas gingivalis outer membrane vesicles divert host innate immunity and promote inflammation via C4′ monophosphorylated lipid A"},"content":{"rendered":"
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J Immunol<\/b>. 2025 Mar 12:vkae050. doi: 10.1093\/jimmun\/vkae050. Online ahead of print.<\/p>\n

ABSTRACT<\/b><\/p>\n

Porphyromonas gingivalis (Pg) is a prevalent pathogen that promotes human periodontal disease (PD) and exacerbates systemic comorbidities such as atherosclerosis, rheumatoid arthritis, and Alzheimer’s disease. Pg produces nonphosphorylated tetra-acylated lipid A (NPLA) in its outer membrane (OM) that evades host Toll-like receptor 4 (TLR4), inflammasome pathways, and cationic peptides, enhancing bacterial survival. Here, we show that Pg also releases outer membrane vesicles (OMVs) that engage and divert host cell TLR4, inflammasome, and LL-37 responses away from the microbe. We determined that Pg OMVs are enriched for C4′ monophosphoryl lipid A (C4′-MPLA), an established agonist for TLR4-TRIF-IFN\u03b2 and inflammasome-IL-1\u03b2 responses. Comparisons of Pg 381 and Pg 33277 stationary phase cultures revealed higher OMV production by Pg 381, which correlates with its higher proinflammatory pathogenicity. The cationic peptide, polymyxin B (PMB), which selectively binds lipid A C4′-phosphate, reduces OMV-stimulated HEK cell TLR4 activation and THP-1 cell IL-1\u03b2 production, confirming the proinflammatory role for OMV-C4′-MPLA. Similar to PMB, the host defense peptide, LL-37, inhibits OMV-C4′-MPLA-dependent HEK cell TLR4 activation. PMB and LL-37 also blocked OMV-C4′-MPLA-driven TLR4 activation in human umbilical vein endothelial cells. Finally, wild-type Pg-containing OM-NPLA is highly resistant to LL-37 antimicrobial activity, whereas the \u0394lpxF mutant bacterium, retaining OM-C4′-MPLA, is killed by the peptide. In summary, Pg escapes host TLR4 signaling, inflammasome activation, and LL-37 interaction by retaining immunoevasive OM-NPLA. Moreover, Pg dispenses proinflammatory OMV-C4′-MPLA, which engages and redirects those host defenses. We suggest that OMV-C4′-MPLA triggers elevated IFN\u03b2 and IL-1\u03b2 cytokines, which typify PD comorbidities, and drive PD-related alveolar bone loss.<\/p>\n

PMID:40131356<\/a> | DOI:10.1093\/jimmun\/vkae050<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

J Immunol. 2025 Mar 12:vkae050. doi: 10.1093\/jimmun\/vkae050. Online ahead of print. ABSTRACT Porphyromonas gingivalis (Pg) is a prevalent pathogen that promotes human periodontal disease (PD) and exacerbates systemic comorbidities such as atherosclerosis, rheumatoid arthritis, and Alzheimer’s disease. Pg produces nonphosphorylated tetra-acylated lipid A (NPLA) in its outer membrane (OM) that evades host Toll-like receptor 4 … 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-28102","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\/28102","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=28102"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/28102\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=28102"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=28102"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=28102"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}