DGAT1-mediated lipid droplet accumulation promotes M. bovis BCG persistence on dendritic cells by acting as an immunoinflammatory platform through PGE₂ signaling

DGAT1-mediated lipid droplet accumulation promotes M. bovis BCG persistence on dendritic cells by acting as an immunoinflammatory platform through PGE₂ signaling | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article DGAT1-mediated lipid droplet accumulation promotes M. bovis BCG persistence on dendritic cells by acting as an immunoinflammatory platform through PGE₂ signaling Guilherme Iack, Jéssica do Prado Valeriano, Vinícius Soares Cardoso, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9407908/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Tuberculosis remains a major global health challenge. In the lungs, dendritic cells (DC)s are among the primary cells infected by Mycobacterium tuberculosis (Mtb), playing a role in initiating adaptive immunity. Mtb exploits host lipid metabolism for survival, particularly using triacylglycerol (TAG) as a carbon source during latency. Here, we investigated the role of TAG synthesis in DC activation and bacterial burden during mycobacterial infection, with a focus on diacylglycerol acyltransferase-1 (DGAT1) and the eicosanoid prostaglandin (PG)E 2 . Bone marrow-derived DCs (BMDC)s from C57BL/6 infected with M. bovis BCG exhibited increased lipid droplet (LD) formation, TAG and cholesterol ester accumulation, and upregulation of the transcription of lipid-related and proinflammatory genes. Pharmacological inhibition of DGAT1 with A922500 reduced bacterial burden, LD accumulation, and mRNA expression of Nos2 , Il1b , and Il6 , as well as the secretion of IL-1β, IL-6, IL-10, IL-23, and TNF-α. However, DGAT1 inhibition did not alter the expression of DC activation markers. Interestingly, PGE 2 secretion was also reduced by inhibition of DGAT-1. Given PGE 2 ’s established role in TB immunity and T cell differentiation, exogenous PGE 2 was added to infected DCs, leading to an increase in bacterial load, cytokine release, and LD accumulation, reversing the effects of DGAT1 inhibition. These findings indicate that TAG synthesis via DGAT1 and PGE 2 signaling are critical modulators of LD formation and the inflammatory response in DCs during mycobacterial infection. lipid droplets tuberculosis BCG dendritic cells triacylglycerol prostaglandin E2 Full Text Additional Declarations No competing interests reported. Supplementary Files msiacketalsupfiles2026.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 08 May, 2026 Reviews received at journal 06 May, 2026 Reviews received at journal 22 Apr, 2026 Reviewers agreed at journal 22 Apr, 2026 Reviewers agreed at journal 22 Apr, 2026 Reviewers agreed at journal 21 Apr, 2026 Reviewers agreed at journal 20 Apr, 2026 Reviewers invited by journal 20 Apr, 2026 Editor assigned by journal 13 Apr, 2026 Submission checks completed at journal 13 Apr, 2026 First submitted to journal 13 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9407908","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":628947430,"identity":"a1822637-245d-4376-adb4-bb14b58919f9","order_by":0,"name":"Guilherme Iack","email":"","orcid":"","institution":"Fluminense Federal University","correspondingAuthor":false,"prefix":"","firstName":"Guilherme","middleName":"","lastName":"Iack","suffix":""},{"id":628947434,"identity":"f794edc7-eff8-4685-999b-858290731cb1","order_by":1,"name":"Jéssica do Prado Valeriano","email":"","orcid":"","institution":"Fluminense Federal University","correspondingAuthor":false,"prefix":"","firstName":"Jéssica","middleName":"do Prado","lastName":"Valeriano","suffix":""},{"id":628947436,"identity":"b7c28f28-f145-41b7-b531-3e7cbbdff808","order_by":2,"name":"Vinícius Soares Cardoso","email":"","orcid":"","institution":"Oswaldo Cruz Foundation","correspondingAuthor":false,"prefix":"","firstName":"Vinícius","middleName":"Soares","lastName":"Cardoso","suffix":""},{"id":628947437,"identity":"022d1ac2-65df-452d-9f9f-960ef7fd6b6b","order_by":3,"name":"Emílio Teles Moreira","email":"","orcid":"","institution":"Oswaldo Cruz Foundation","correspondingAuthor":false,"prefix":"","firstName":"Emílio","middleName":"Teles","lastName":"Moreira","suffix":""},{"id":628947439,"identity":"f5ce703c-7c72-4de8-b206-39ff24089c67","order_by":4,"name":"Matheus A. 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In the lungs, dendritic cells (DC)s are among the primary cells infected by \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e (Mtb), playing a role in initiating adaptive immunity. Mtb exploits host lipid metabolism for survival, particularly using triacylglycerol (TAG) as a carbon source during latency. Here, we investigated the role of TAG synthesis in DC activation and bacterial burden during mycobacterial infection, with a focus on diacylglycerol acyltransferase-1 (DGAT1) and the eicosanoid prostaglandin (PG)E\u003csub\u003e2\u003c/sub\u003e. Bone marrow-derived DCs (BMDC)s from C57BL/6 infected with \u003cem\u003eM. bovis\u003c/em\u003e BCG exhibited increased lipid droplet (LD) formation, TAG and cholesterol ester accumulation, and upregulation of the transcription of lipid-related and proinflammatory genes. Pharmacological inhibition of DGAT1 with A922500 reduced bacterial burden, LD accumulation, and mRNA expression of \u003cem\u003eNos2\u003c/em\u003e, \u003cem\u003eIl1b\u003c/em\u003e, and \u003cem\u003eIl6\u003c/em\u003e, as well as the secretion of IL-1β, IL-6, IL-10, IL-23, and TNF-α. However, DGAT1 inhibition did not alter the expression of DC activation markers. Interestingly, PGE\u003csub\u003e2\u003c/sub\u003e secretion was also reduced by inhibition of DGAT-1. Given PGE\u003csub\u003e2\u003c/sub\u003e\u0026rsquo;s established role in TB immunity and T cell differentiation, exogenous PGE\u003csub\u003e2\u003c/sub\u003e was added to infected DCs, leading to an increase in bacterial load, cytokine release, and LD accumulation, reversing the effects of DGAT1 inhibition. These findings indicate that TAG synthesis via DGAT1 and PGE\u003csub\u003e2\u003c/sub\u003e signaling are critical modulators of LD formation and the inflammatory response in DCs during mycobacterial infection.\u003c/p\u003e","manuscriptTitle":"DGAT1-mediated lipid droplet accumulation promotes M. bovis BCG persistence on dendritic cells by acting as an immunoinflammatory platform through PGE₂ signaling","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-28 16:26:33","doi":"10.21203/rs.3.rs-9407908/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-09T01:56:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T19:02:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-23T03:03:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"230623246355568079165864970593046081733","date":"2026-04-23T01:32:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"251260674256138545155389046725720552991","date":"2026-04-22T20:30:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"289245320775321406318577010272465785083","date":"2026-04-21T04:53:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"250640728531610839168243732557271240492","date":"2026-04-20T16:19:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-20T15:56:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-14T03:45:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-14T03:45:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"Inflammation","date":"2026-04-13T19:23:23+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"inflammation","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ifla","sideBox":"Learn more about [Inflammation](https://www.springer.com/journal/10753)","snPcode":"10753","submissionUrl":"https://submission.nature.com/new-submission/10753/3","title":"Inflammation","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d50f138a-4624-41ee-84b5-954c5443330e","owner":[],"postedDate":"April 28th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-09T01:56:35+00:00","index":40,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T19:02:05+00:00","index":39,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-28T16:26:33+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-28 16:26:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9407908","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9407908","identity":"rs-9407908","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}