{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T11:57:18Z","timestamp":1775735838274,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFD1800800"],"award-info":[{"award-number":["2021YFD1800800"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172850"],"award-info":[{"award-number":["32172850"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32102684"],"award-info":[{"award-number":["32102684"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Streptococcus pneumoniae<\/jats:italic> is an invasive pathogen with high morbidity and mortality in the immunocompromised children and elderly. NOD-like receptor family pyrin domain containing 6 (NLRP6) plays an important role in the host innate immune response against pathogen infections. Our previous studies have shown that NLRP6 plays a negative regulatory role in host defense against <jats:italic>S. pneumoniae<\/jats:italic>, but the underlying mechanism is still unclear. The further negative regulatory role of NLRP6 in the host was investigated in this study. Our results showed that NLRP6<jats:sup>\u2212\/\u2212<\/jats:sup> mice in the lung had lower bacterial burdens after <jats:italic>S. pneumoniae<\/jats:italic> infection and expressed higher level of tight junction (TJ) protein occludin compared to WT mice, indicating the detrimental role of NLRP6 in the host defense against <jats:italic>S. pneumoniae<\/jats:italic> infection. Transcriptome analysis showed that genes related to leukocytes migration and recruitment were differentially expressed between wild-type (WT) and NLRP6 knockout (NLRP6<jats:sup>\u2212\/\u2212<\/jats:sup>) mice during <jats:italic>S. pneumoniae<\/jats:italic> infection. Also, NLRP6<jats:sup>\u2212\/\u2212<\/jats:sup> mice showed higher expression of chemokines including C-X-C motif chemokine ligand 1 (CXCL1) and 2 (CXCL2) and lower gene expression of complement C3a receptor 1 (C3aR1) and P-selectin glycoprotein ligand-1 (PSGL-1) which are the factors that inhibit the recruitment of neutrophils. Furthermore, NLRP6<jats:sup>\u2212\/\u2212<\/jats:sup> neutrophils showed increased intracellular bactericidal ability and the formation of neutrophil extracellular traps (NETs) during <jats:italic>S. pneumoniae<\/jats:italic> infection. Taken together, our study suggests that NLRP6 is a negative regulator of neutrophil recruitment and function during <jats:italic>S. pneumoniae<\/jats:italic> infection. Our study provides a new insight to develop novel strategies to treat invasive pneumococcal infection.<\/jats:p>","DOI":"10.3389\/fmicb.2022.898559","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T09:30:38Z","timestamp":1653471038000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["NLRP6 Serves as a Negative Regulator of Neutrophil Recruitment and Function During Streptococcus pneumoniae Infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Qi","family":"Tao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongyi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaixiang","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinrui","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanlei","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Liang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianci","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rendong","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/nature11250","article-title":"NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens","volume":"488","author":"Anand","year":"2012","journal-title":"Nature"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1126\/science.aaf7419","article-title":"A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion","volume":"352","author":"Birchenough","year":"2016","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"110202","DOI":"10.1016\/j.celrep.2021.110202","article-title":"Dysregulation of Streptococcus pneumoniae zinc homeostasis breaks ampicillin resistance in a pneumonia infection model","volume":"38","author":"Brazel","year":"2022","journal-title":"Cell Rep."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e98254","DOI":"10.1172\/jci.insight.98254","article-title":"Complement receptor C3aR1 controls neutrophil mobilization following spinal cord injury through physiological antagonism of CXCR2","volume":"4","author":"Brennan","year":"2019","journal-title":"JCI Insight"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil extracellular traps kill bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1038\/s41385-020-00357-4","article-title":"NLRP6 modulates neutrophil homeostasis in bacterial pneumonia-derived sepsis","volume":"14","author":"Cai","year":"2021","journal-title":"Mucosal Immunol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.3389\/fimmu.2020.01259","article-title":"Multiple roles for chemokines in neutrophil biology","volume":"11","author":"Capucetti","year":"2020","journal-title":"Front. 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