{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T09:42:10Z","timestamp":1793871730242,"version":"4.6.1"},"reference-count":62,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":60,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-156291"],"award-info":[{"award-number":["PJT-156291"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:p>\n                    Individuals with clonal hematopoiesis of indeterminate potential (CHIP) are at increased risk of aging related health conditions and all-cause mortality, but whether CHIP affects risk of infection is much less clear. Using UK Biobank data, we revealed a positive association between CHIP and incident pneumonia in 438,421 individuals. We show that inflammation enhanced pneumonia risk, as CHIP carriers with a hypomorphic IL6 receptor polymorphism were protected. To better characterize the pathways of susceptibility, we challenged hematopoietic\n                    <jats:italic>Tet Methylcytosine Dioxygenase 2\u2013<\/jats:italic>\n                    knockout (\n                    <jats:italic>\n                      Tet2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ) and floxed control mice (\n                    <jats:italic>\n                      Tet2\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    ) with\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    . As with human CHIP carriers,\n                    <jats:italic>\n                      Tet2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice had hematopoietic abnormalities resulting in the expansion of inflammatory monocytes and neutrophils in peripheral blood. Yet, these cells were insufficient in defending against\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>pneumoniae<\/jats:italic>\n                    and resulted in increased pathology, impaired bacterial clearance, and higher mortality in\n                    <jats:italic>\n                      Tet2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. We delineated the transcriptional landscape of\n                    <jats:italic>\n                      Tet2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    neutrophils and found that, while inflammation-related pathways were upregulated in\n                    <jats:italic>\n                      Tet2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    neutrophils, migration and motility pathways were compromised. Using live-imaging techniques, we demonstrated impairments in motility, pathogen uptake, and neutrophil extracellular trap (NET) formation by\n                    <jats:italic>\n                      Tet2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    neutrophils. Collectively, we show that CHIP is a risk factor for bacterial pneumonia related to innate immune impairments.\n                  <\/jats:p>","DOI":"10.1172\/jci171002","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T12:58:26Z","timestamp":1712235506000},"source":"Crossref","is-referenced-by-count":30,"title":["Neutrophil-mediated innate immune resistance to bacterial pneumonia is dependent on Tet2 function"],"prefix":"10.1172","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7339-6059","authenticated-orcid":true,"given":"Candice","family":"Quin","sequence":"first","affiliation":[{"name":"Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada."},{"name":"Firestone Institute for Respiratory Health, St. Joseph\u2019s Healthcare, Hamilton, Ontario, Canada."},{"name":"Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United 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Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlyn","family":"Vlasschaert","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Faculty of Health Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2797-2283","authenticated-orcid":true,"given":"Sanathan","family":"Sadh","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Faculty of Health Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy J.M.","family":"McNaughton","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Faculty of Health Sciences,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9584-9861","authenticated-orcid":true,"given":"Marco M.","family":"Buttigieg","sequence":"additional","affiliation":[{"name":"Department of Pathology and 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