{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T15:37:46Z","timestamp":1772638666638,"version":"3.50.1"},"posted":{"date-parts":[[2026,2,28]]},"group-title":"Immunology","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National institute of health","award":["1R01AI152337"],"award-info":[{"award-number":["1R01AI152337"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Macrophage antimicrobial programs are regulated not only by transcriptional networks but also by RNA processing mechanisms affecting signal transduction and effector responses. One such mechanism, alternative polyadenylation (APA), determines mRNA fate by changing the length of the 3\u02b9 UTR. However, our understanding of the impact of APA on antibacterial functions and how we can manipulate it to influence infection outcomes remains limited. In this study, we identify the APA regulator CFIm25 (NUDT21) as a promoter of macrophage defense against\n                  <jats:italic>Salmonella enterica<\/jats:italic>\n                  serovar Typhimurium (STM). STM infection is known to drive macrophages toward an M2-like immunosuppressive state conducive to bacterial survival. Concurrent with this transition, the CFIm25 level is reduced, and the 3\u2019 UTRs of CFIm25 targets encoding key immune proteins, such as TAB2 and TBL1XR1, are lengthened, suggesting a role for APA changes in the response to STM. Overexpression of CFIm25 in infected macrophages blocks these\n                  <jats:italic>Salmonella<\/jats:italic>\n                  -induced 3\u2019 UTR changes, leading to greater mRNA and protein expression. Significantly, the increase in CFIm25 suppresses infection, thereby creating a more antimicrobial intracellular environment, improving macrophage survival, and reducing M2 properties that support bacterial replication. Specifically, CFIm25 enhances production of the antibacterial peptide LL-37, increases reactive oxygen species and nitric oxide levels, suppresses arginase activity and lactate production, and stimulates release of pro-inflammatory cytokines while inhibiting anti-inflammatory cytokines. Depletion studies show TAB2 mediates CFIm25\u2019s antibacterial effects by activating both MAPK and NF-kB pathways. Our findings highlight APA regulation as a potential target for boosting immune defenses and developing treatments for chronic bacterial infections.\n                <\/jats:p>","DOI":"10.64898\/2026.02.26.707986","type":"posted-content","created":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T02:50:13Z","timestamp":1772333413000},"source":"Crossref","is-referenced-by-count":0,"title":["The Alternative Polyadenylation Factor CFIm25 Orchestrates Macrophage Antibacterial Immunity by Amplifying TAB2-Mediated MAPK and NF-\u03baB Signaling During\n                  <i>Salmonella<\/i>\n                  Infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9425-4252","authenticated-orcid":false,"given":"Atish","family":"Barua","sequence":"first","affiliation":[{"name":"Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7521-2812","authenticated-orcid":false,"given":"Srimoyee","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"Department of Biology & Biotechnology, Worcester Polytechnic Institute, 60 Prescott Street, Worcester, Massachusetts 01601, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1883-9459","authenticated-orcid":false,"given":"Claire L.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026030401500826000_2026.02.26.707986v1.1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41577-024-01080-y","article-title":"Inducible antibacterial responses in macrophages","volume":"25","year":"2025","journal-title":"Nat Rev Immunol"},{"key":"2026030401500826000_2026.02.26.707986v1.2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26052107"},{"key":"2026030401500826000_2026.02.26.707986v1.3","doi-asserted-by":"crossref","first-page":"e658","DOI":"10.1002\/mco2.658","article-title":"Macrophage plasticity: signaling pathways, tissue repair, and regeneration","volume":"5","year":"2024","journal-title":"MedComm"},{"key":"2026030401500826000_2026.02.26.707986v1.4","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.3390\/ijms26062611","article-title":"Salmonella Type III Secretion System Effectors","volume":"26","year":"2025","journal-title":"Int J Mol Sci"},{"key":"2026030401500826000_2026.02.26.707986v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2023.105128"},{"key":"2026030401500826000_2026.02.26.707986v1.6","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1021\/acsinfecdis.4c00270","article-title":"Decoding Bacterial Persistence: Mechanisms and Strategies for Effective Eradication","volume":"10","year":"2024","journal-title":"ACS Infect Dis"},{"key":"2026030401500826000_2026.02.26.707986v1.7","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2025.2449775"},{"issue":"12","key":"2026030401500826000_2026.02.26.707986v1.8","first-page":"818668","article-title":"The Role of Alternative Polyadenylation in the Regulation of Subcellular RNA Localization","volume":"14","year":"2022","journal-title":"Front Genet"},{"key":"2026030401500826000_2026.02.26.707986v1.9","doi-asserted-by":"crossref","unstructured":"Tian B , Yu S , Zhang Q . 2026. 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