{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T14:29:41Z","timestamp":1769264981315,"version":"3.49.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI104732"],"award-info":[{"award-number":["R01 AI104732"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Asplenia imparts susceptibility to life-threatening sepsis with encapsulated bacteria, such as the pneumococcus. However, the cellular components within the splenic environment that guard against pneumococcal bacteremia have not been defined. The actin-bundling protein L-plastin (LPL) is essential for the generation of marginal zone B cells and for anti-pneumococcal host defense, as revealed by a mouse model of genetic LPL deficiency. In independent studies, serine phosphorylation of LPL at residue 5 (S5) has been described as a key \u201cswitch\u201d in regulating LPL actin binding and subsequent cell motility, although much of the data are correlative. To test the importance of S5 phosphorylation in LPL function, and to specifically assess the requirement of LPL S5 phosphorylation in anti-pneumococcal host defense, we generated the \u201cS5A\u201d mouse, expressing endogenous LPL bearing a serine-to-alanine mutation at this position. S5A mice were bred to homozygosity, and LPL was expressed at levels equivalent to wild-type, but S5 phosphorylation was absent. S5A mice exhibited specific impairment in clearance of pneumococci following i.v. challenge, with 10-fold-higher bacterial bloodstream burden 24 h after challenge compared with wild-type or fully LPL-deficient animals. Defective bloodstream clearance correlated with diminished population of marginal zone macrophages and with reduced phagocytic capacity of multiple innate immune cells. Development and function of other tested leukocyte lineages, such as T and B cell motility and activation, were normal in S5A mice. The S5A mouse thus provides a novel system in which to elucidate the precise molecular control of critical immune cell functions in specific host\u2013pathogen defense interactions.<\/jats:p>","DOI":"10.4049\/jimmunol.2000899","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T17:14:19Z","timestamp":1618506859000},"page":"2135-2145","source":"Crossref","is-referenced-by-count":8,"title":["Novel Mouse Model Reveals That Serine Phosphorylation of L-Plastin Is Essential for Effective Splenic Clearance of Pneumococcus"],"prefix":"10.1093","volume":"206","author":[{"given":"Edgar P","family":"Anaya","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Washington University School of Medicine , St. Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Washington University School of Medicine , St. Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2342-1097","authenticated-orcid":false,"given":"Elizabeth M","family":"Todd","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Washington University School of Medicine , St. Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor P","family":"Szasz","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Washington University School of Medicine , St. Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0121","authenticated-orcid":false,"given":"S Celeste","family":"Morley","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Washington University School of Medicine , St. Louis, MO"},{"name":"Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine , St. Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"2025030417503193600_r1","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/S0140-6736(09)61204-6","article-title":"Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates","volume":"374","author":"O\u2019Brien","year":"2009","journal-title":"Lancet"},{"key":"2025030417503193600_r2","first-page":"470","article-title":"Severe pneumococcal pneumonia: new strategies for management","volume":"12","author":"Chiou","year":"2006","journal-title":"Curr. 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