{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:21:45Z","timestamp":1785417705783,"version":"3.56.0"},"posted":{"date-parts":[[2026,2,2]]},"group-title":"Immunology","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["U19 AI142784"],"award-info":[{"award-number":["U19 AI142784"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32 AI007520"],"award-info":[{"award-number":["T32 AI007520"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32 HL098040"],"award-info":[{"award-number":["T32 HL098040"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Tuberculosis (TB) remains one of the leading causes of death from a single infectious agent worldwide, yet the host pathways that regulate antigen presentation and lung inflammation during\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  (Mtb) infection are incompletely defined. Sorting nexin 5 (SNX5) is a protein best known for roles in endosomal trafficking, antigen processing, and antiviral host defense, but its contribution to immunity during Mtb infection is unknown. Here, we show that SNX5-deficient mice exhibit markedly increased mortality following low-dose aerosol infection despite unchanged pulmonary bacterial burden compared to wild-type mice.\n                  <jats:italic>Snx5<\/jats:italic>\n                  <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  mice developed exacerbated lung inflammation without major alterations in immune cell recruitment. In macrophages,\n                  <jats:italic>Snx5<\/jats:italic>\n                  did not affect phagocytosis, vacuolar maturation, intracellular bacterial control, or global transcriptional responses to Mtb, but was required for efficient MHC class II antigen presentation.\n                  <jats:italic>Snx5<\/jats:italic>\n                  deficiency reduced antigen degradation, limited peptide loading onto MHC-II and impaired activation of antigen-specific CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells without altering surface MHC-II abundance or expression of costimulatory molecules. Together, these findings identify SNX5 as a previously unrecognized regulator of MHC-II peptide loading that shapes inflammatory outcomes during pulmonary Mtb infection, highlighting a role for the endosomal sorting machinery in immunity to intracellular pathogens.\n                <\/jats:p>","DOI":"10.64898\/2026.01.30.702915","type":"posted-content","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T04:40:15Z","timestamp":1770093615000},"source":"Crossref","is-referenced-by-count":0,"title":["Sorting nexin 5 mediates antigen presentation and immunity against\n                  <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7433-3869","authenticated-orcid":false,"given":"Beatriz R. S.","family":"Dias","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4703-9466","authenticated-orcid":false,"given":"Kubra F.","family":"Naqvi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1276-6563","authenticated-orcid":false,"given":"Victoria A.","family":"Ektnitphong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-6078","authenticated-orcid":false,"given":"Samuel","family":"Alvarez-Arguedas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8101-5604","authenticated-orcid":false,"given":"Kathryn C.","family":"Rahlwes","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1789-3290","authenticated-orcid":false,"given":"Priscila C.","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4329-2253","authenticated-orcid":false,"given":"Michael U.","family":"Shiloh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA"},{"name":"Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026020605450649000_2026.01.30.702915v1.1","unstructured":"WHO, Global tuberculosis report 2025. 2025: Geneva: World Health Organization. p. License: CC BY-NC-SA 3.0 IGO."},{"key":"2026020605450649000_2026.01.30.702915v1.2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03510330076038"},{"key":"2026020605450649000_2026.01.30.702915v1.3","doi-asserted-by":"crossref","first-page":"117594","DOI":"10.1016\/j.lfs.2020.117594","article-title":"Tuberculosis vaccine: A journey from BCG to present","volume":"252","year":"2020","journal-title":"Life Sci"},{"key":"2026020605450649000_2026.01.30.702915v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60410-2"},{"key":"2026020605450649000_2026.01.30.702915v1.5","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.612675"},{"key":"2026020605450649000_2026.01.30.702915v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00731-y"},{"key":"2026020605450649000_2026.01.30.702915v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/35085034"},{"key":"2026020605450649000_2026.01.30.702915v1.8","doi-asserted-by":"publisher","DOI":"10.1042\/bj20020691"},{"issue":"1","key":"2026020605450649000_2026.01.30.702915v1.9","doi-asserted-by":"crossref","first-page":"2150449","DOI":"10.1080\/21505594.2022.2150449","article-title":"Pathogenicity and virulence of Mycobacterium tuberculosis","volume":"14","year":"2023","journal-title":"Virulence"},{"key":"2026020605450649000_2026.01.30.702915v1.10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409716102"},{"key":"2026020605450649000_2026.01.30.702915v1.11","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05987-11"},{"key":"2026020605450649000_2026.01.30.702915v1.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2423292122"},{"key":"2026020605450649000_2026.01.30.702915v1.13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0070514"},{"key":"2026020605450649000_2026.01.30.702915v1.14","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2101-2110.2004"},{"key":"2026020605450649000_2026.01.30.702915v1.15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.2.910"},{"key":"2026020605450649000_2026.01.30.702915v1.16","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.10.1421"},{"key":"2026020605450649000_2026.01.30.702915v1.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002052"},{"key":"2026020605450649000_2026.01.30.702915v1.18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080353"},{"key":"2026020605450649000_2026.01.30.702915v1.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801496105"},{"key":"2026020605450649000_2026.01.30.702915v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2014.06.003"},{"key":"2026020605450649000_2026.01.30.702915v1.21","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12274"},{"key":"2026020605450649000_2026.01.30.702915v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.03.010"},{"key":"2026020605450649000_2026.01.30.702915v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-3879(48)80033-4"},{"issue":"10","key":"2026020605450649000_2026.01.30.702915v1.24","doi-asserted-by":"crossref","first-page":"e0140852","DOI":"10.1371\/journal.pone.0140852","article-title":"Functional Impairment of Myeloid Dendritic Cells during Advanced Stage of HIV-1 Infection: Role of Factors Regulating Cytokine Signaling","volume":"10","year":"2015","journal-title":"PLoS One"},{"key":"2026020605450649000_2026.01.30.702915v1.25","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.8.4501-4509.2002"},{"key":"2026020605450649000_2026.01.30.702915v1.26","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071367"},{"key":"2026020605450649000_2026.01.30.702915v1.27","doi-asserted-by":"crossref","unstructured":"Upadhyay, S. , E. Mittal , and J.A. Philips , Tuberculosis and the art of macrophage manipulation. Pathog Dis, 2018. 76(4).","DOI":"10.1093\/femspd\/fty037"},{"key":"2026020605450649000_2026.01.30.702915v1.28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00705.x"},{"key":"2026020605450649000_2026.01.30.702915v1.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401657101"},{"key":"2026020605450649000_2026.01.30.702915v1.30","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01872-06"},{"key":"2026020605450649000_2026.01.30.702915v1.31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.20.13326"},{"key":"2026020605450649000_2026.01.30.702915v1.32","doi-asserted-by":"publisher","DOI":"10.1126\/science.8303277"},{"key":"2026020605450649000_2026.01.30.702915v1.33","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.2000.1633"},{"key":"2026020605450649000_2026.01.30.702915v1.34","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/405310"},{"key":"2026020605450649000_2026.01.30.702915v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.283"},{"key":"2026020605450649000_2026.01.30.702915v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2374"},{"key":"2026020605450649000_2026.01.30.702915v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2427"},{"key":"2026020605450649000_2026.01.30.702915v1.38","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201703015"},{"key":"2026020605450649000_2026.01.30.702915v1.39","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201702137"},{"key":"2026020605450649000_2026.01.30.702915v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2012.09.001"},{"key":"2026020605450649000_2026.01.30.702915v1.41","doi-asserted-by":"publisher","DOI":"10.1042\/bss0720223"},{"key":"2026020605450649000_2026.01.30.702915v1.42","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200312055"},{"key":"2026020605450649000_2026.01.30.702915v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-00861-8"},{"key":"2026020605450649000_2026.01.30.702915v1.44","doi-asserted-by":"publisher","DOI":"10.1242\/bio.20122204"},{"key":"2026020605450649000_2026.01.30.702915v1.45","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003879"},{"key":"2026020605450649000_2026.01.30.702915v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03056-z"},{"key":"2026020605450649000_2026.01.30.702915v1.47","doi-asserted-by":"publisher","DOI":"10.1186\/2045-9912-2-30"},{"key":"2026020605450649000_2026.01.30.702915v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.05.005"},{"key":"2026020605450649000_2026.01.30.702915v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.11.002"},{"key":"2026020605450649000_2026.01.30.702915v1.50","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12263"},{"key":"2026020605450649000_2026.01.30.702915v1.51","doi-asserted-by":"crossref","unstructured":"Khan, H.S. , et al., Identification of scavenger receptor B1 as the airway microfold cell receptor for Mycobacterium tuberculosis. Elife, 2020. 9.","DOI":"10.7554\/eLife.52551"},{"key":"2026020605450649000_2026.01.30.702915v1.52","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.isci.2018.12.015","article-title":"The Phosphoinositide Kinase PIKfyve Promotes Cathepsin-S-Mediated Major Histocompatibility Complex Class II Antigen Presentation","volume":"11","year":"2019","journal-title":"iScience"},{"key":"2026020605450649000_2026.01.30.702915v1.53","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2486-6"},{"key":"2026020605450649000_2026.01.30.702915v1.54","doi-asserted-by":"crossref","unstructured":"Tzelepis, F ., et al., Mitochondrial cyclophilin D regulates T cell metabolic responses and disease tolerance to tuberculosis. Sci Immunol, 2018. 3(23).","DOI":"10.1126\/sciimmunol.aar4135"},{"key":"2026020605450649000_2026.01.30.702915v1.55","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201344219"},{"key":"2026020605450649000_2026.01.30.702915v1.56","doi-asserted-by":"publisher","DOI":"10.1111\/TRA.12885"},{"key":"2026020605450649000_2026.01.30.702915v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/nrm974"},{"key":"2026020605450649000_2026.01.30.702915v1.58","doi-asserted-by":"crossref","unstructured":"Cabrera-Reyes, F. , et al., SNX5 promotes antigen presentation in B cells by dual regulation of actin and lysosomal dynamics. Life Sci Alliance, 2025. 8(1).","DOI":"10.26508\/lsa.202402917"},{"issue":"10","key":"2026020605450649000_2026.01.30.702915v1.59","doi-asserted-by":"crossref","first-page":"e47585","DOI":"10.1371\/journal.pone.0047585","article-title":"Flanking residues are central to DO11.10 T cell hybridoma stimulation by ovalbumin 323-339","volume":"7","year":"2012","journal-title":"PLoS One"},{"key":"2026020605450649000_2026.01.30.702915v1.60","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.9.4706"},{"key":"2026020605450649000_2026.01.30.702915v1.61","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.32"},{"key":"2026020605450649000_2026.01.30.702915v1.62","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2007.05.020"},{"key":"2026020605450649000_2026.01.30.702915v1.63","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800202"},{"key":"2026020605450649000_2026.01.30.702915v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2015.06.004"},{"key":"2026020605450649000_2026.01.30.702915v1.65","doi-asserted-by":"crossref","unstructured":"Yong, X. , et al., SNX27-FERM-SNX1 complex structure rationalizes divergent trafficking pathways by SNX17 and SNX27. Proc Natl Acad Sci U S A, 2021. 118(36).","DOI":"10.1073\/pnas.2105510118"},{"key":"2026020605450649000_2026.01.30.702915v1.66","doi-asserted-by":"crossref","unstructured":"Soreng, K. , et al., SNX18 regulates ATG9A trafficking from recycling endosomes by recruiting Dynamin-2. EMBO Rep, 2018. 19(4).","DOI":"10.15252\/embr.201744837"},{"issue":"6","key":"2026020605450649000_2026.01.30.702915v1.67","doi-asserted-by":"crossref","first-page":"e1009607","DOI":"10.1371\/journal.pgen.1009607","article-title":"SNX-3 mediates retromer-independent tubular endosomal recycling by opposing EEA-1-facilitated trafficking","volume":"17","year":"2021","journal-title":"PLoS Genet"},{"issue":"11","key":"2026020605450649000_2026.01.30.702915v1.68","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/s41423-019-0285-2","article-title":"SNX8 modulates the innate immune response to RNA viruses by regulating the aggregation of VISA","volume":"17","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"2026020605450649000_2026.01.30.702915v1.69","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402734"},{"key":"2026020605450649000_2026.01.30.702915v1.70","doi-asserted-by":"publisher","DOI":"10.1038\/nri3818"},{"key":"2026020605450649000_2026.01.30.702915v1.71","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-208439"},{"issue":"17","key":"2026020605450649000_2026.01.30.702915v1.72","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/s41388-025-03298-z","article-title":"SNX5 facilitates the progression of gastric cancer by increasing the membrane localization of LRP5","volume":"44","year":"2025","journal-title":"Oncogene"},{"issue":"6","key":"2026020605450649000_2026.01.30.702915v1.73","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1038\/s41564-025-01988-8","article-title":"ATG5 suppresses type I IFN-dependent neutrophil effector functions during Mycobacterium tuberculosis infection in mice","volume":"10","year":"2025","journal-title":"Nat Microbiol"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.01.30.702915","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T13:45:15Z","timestamp":1770385515000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.01.30.702915"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":73,"URL":"https:\/\/doi.org\/10.64898\/2026.01.30.702915","relation":{},"subject":[],"published":{"date-parts":[[2026,2,2]]},"subtype":"preprint"}}