{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:02:09Z","timestamp":1784523729925,"version":"3.55.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pneumococcal serotype 1 (sequence type 217) is a leading cause of invasive disease outbreaks in Sub-Saharan Africa, causing significant morbidity and mortality. Understanding the transmission dynamics of hypervirulent strains such as ST217 is key to developing therapies and vaccines that can reduce outbreak incidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The transmission dynamics of ST217 were investigated using an adolescent mouse pneumococcal transmission model, representing the population mainly affected by disease outbreaks in Sub-Saharan Africa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that TNF receptor-2 (TNFR2)-positive regulatory T-cells (Tregs) paradoxically create the conditions that promote ST217 transmission. During ST217 colonisation, TNFR2\n                      <jats:sup>+<\/jats:sup>\n                      Tregs accumulate in the nasopharynx and suppress IL-17A-producing \u03b3\u03b4T and Th17 cells, leading to reduced neutrophil-mediated pneumococcal clearance. This attenuated inflammatory response increases ST217 carriage density, consequently increasing nasal shedding to levels that increase transmission. Furthermore, we show that these TNFR2\n                      <jats:sup>+<\/jats:sup>\n                      Treg responses are strain-dependent and driven by the pneumococcal toxin pneumolysin. The low-transmission serotype 23F exhibits low pneumolysin activity, resulting in impaired TNFR2\n                      <jats:sup>+<\/jats:sup>\n                      Treg responses. This, in turn, enhances activation of the \u03b3\u03b4T17-neutrophil axis, which promotes pneumococcal clearance and disrupts 23F transmission.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study demonstrates an unexpected but key role of TNFR2\n                      <jats:sup>+<\/jats:sup>\n                      Tregs in transmission of hypervirulent pneumococci.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1840694","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T04:21:18Z","timestamp":1784521278000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pneumococcal transmission is driven by TNFR2+ regulatory 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