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Our understanding of the associated mechanisms is limited to thymus-independent (TI) antibody production by the marginal zone (MZ) B cells, leaving the contribution of other splenic compartments such as the red pulp (RP) largely unexplored despite asplenic patients succumbing to the infection in the first 24 h, suggesting important antibody-independent mechanisms. In this study, using time-lapse intravital imaging of the spleen, we identify a tropism for Streptococcus pneumoniae in this organ mediated by tissue-resident MZ and RP macrophages and a protective role for two distinct splenic neutrophil populations (Ly6Ghi and Ly6Gintermediate) residing in the splenic RP. Splenic mature neutrophils mediated pneumococcal clearance in the spleen by plucking bacteria off the surface of RP macrophages that caught the majority of bacteria in a complement-dependent manner. This neutrophil phagocytic capacity was further enhanced after TI antibody production. Resident immature neutrophils (Ly6Gintermediate) in the spleen undergo emergency proliferation and mobilization from their splenic niche after pneumococcal stimulation to increase the effector mature neutrophil pool. We demonstrate that splenic neutrophils together with two macrophage populations and MZ B cells regulate systemic S. pneumoniae clearance through complementary mechanisms.<\/jats:p>","DOI":"10.1084\/jem.20161621","type":"journal-article","created":{"date-parts":[[2017,4,19]],"date-time":"2017-04-19T10:10:16Z","timestamp":1492596616000},"page":"1333-1350","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":229,"title":["Splenic Ly6Ghigh mature and Ly6Gint immature neutrophils contribute to eradication of\n                    <i>S. pneumoniae<\/i>"],"prefix":"10.1084","volume":"214","author":[{"given":"Justin F.","family":"Deniset","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada 1"},{"name":"Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0519-1227","authenticated-orcid":true,"given":"Bas G.","family":"Surewaard","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada 1"},{"name":"Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada 3"},{"name":"Department of Medical Microbiology, University Medical Centre, 3584 CX Utrecht, Netherlands 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4702-8540","authenticated-orcid":true,"given":"Woo-Yong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada 1"},{"name":"Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2835-4244","authenticated-orcid":true,"given":"Paul","family":"Kubes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada 1"},{"name":"Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada 2"},{"name":"Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2017,4,19]]},"reference":[{"key":"2023072603571721500_bib1","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1038\/nn2014","article-title":"Local self-renewal can sustain CNS microglia maintenance and function throughout adult life","volume":"10","author":"Ajami","year":"2007","journal-title":"Nat. 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