{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:03:34Z","timestamp":1793153014006,"version":"4.5.0"},"posted":{"date-parts":[[2023,8,24]]},"group-title":"Microbiology","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T00:00:00Z","timestamp":1692835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,18]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  The\n                  <jats:italic>ALDH2*2<\/jats:italic>\n                  (rs671) variant present in &gt;500 million individuals reduces ALDH2 function, impairing aldehyde detoxification. While aldehyde accumulation in these individuals is associated with numerous negative health consequences, a previous study showed a cohort of\n                  <jats:italic>ALDH2*2<\/jats:italic>\n                  carriers are less likely to develop active pulmonary tuberculosis. Here, we present additional human data that support this finding and show ALDH2-deficiency in mice provides a fitness advantage during bacterial infections. We found aldehydes normally detoxified by ALDH2 killed the bacterial pathogens\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  and\n                  <jats:italic>Francisella tularensis.<\/jats:italic>\n                  Infected macrophages from\n                  <jats:italic>\n                    Aldh2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  mice had higher levels of formaldehyde and 4-hydroxynonenal, which enhanced their microbicidal capacity.\n                  <jats:italic>\n                    Aldh2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                  <\/jats:italic>\n                  mice were more resistant to infection with\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  and\n                  <jats:italic>Francisella tularensis<\/jats:italic>\n                  than parental mice and displayed elevated inflammatory cytokine and chemokine levels, accompanied by an increased accumulation of inflammatory monocytes and macrophages. These findings support a model in which host-derived aldehydes are robust innate immune effectors, limiting bacterial infection through both direct microbicidal activity and immune modulation. Collectively, this work may explain why the\n                  <jats:italic>ALDH2*2<\/jats:italic>\n                  allele was selected for in humans.\n                <\/jats:p>","DOI":"10.1101\/2023.08.24.554661","type":"posted-content","created":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T00:10:14Z","timestamp":1692922214000},"source":"Crossref","is-referenced-by-count":16,"title":["Impaired aldehyde detoxification caused by a common human polymorphism promotes anti-bacterial immunity"],"prefix":"10.64898","author":[{"given":"Scott","family":"Espich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Berry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Balakhmet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuling","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen T.T.","family":"Thuong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajkumar","family":"Dorajoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiea-Chuen","family":"Khor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chew-Kiat","family":"Heng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Min","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woon-Puay","family":"Koh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Anaya-Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Tenney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rishika","family":"Baral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7843-1503","authenticated-orcid":false,"given":"Dmitri I.","family":"Kotov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marietta","family":"Ravesloot-Chavez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6686-3912","authenticated-orcid":false,"given":"Russell E.","family":"Vance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Dunstan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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