{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:27:40Z","timestamp":1790184460566,"version":"4.1.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>CCR2 is the major chemokine receptor that regulates appropriate trafficking of inflammatory monocytes, but the role of this chemokine receptor and its ligands during primary and secondary infection with intracellular infections remains incompletely understood. Here we used murine infection with the Live Vaccine Strain (LVS) of <jats:italic>Francisella tularensis<\/jats:italic> to evaluate the role of CCR2 during primary and secondary parenteral responses to this prototype intracellular bacterium. We find that mice deficient in CCR2 are highly compromised in their ability to survive intradermal infection with LVS, indicating the importance of this receptor during primary parenteral responses. Interestingly, this defect could not be readily attributed to the activities of the known murine CCR2 ligands MCP-1\/CCL2, MCP-3\/CCL7, or MCP-5\/CCL12. Nonetheless, CCR2 knockout mice vaccinated by infection with low doses of LVS generated optimal T cell responses that controlled the intramacrophage replication of <jats:italic>Francisella<\/jats:italic>, and LVS-immune CCR2 knockout mice survived maximal lethal <jats:italic>Francisella<\/jats:italic> challenge. Thus, fully protective adaptive immune memory responses to this intracellular bacterium can be readily generated in the absence of CCR2.<\/jats:p>","DOI":"10.1371\/journal.pone.0249142","type":"journal-article","created":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T17:44:15Z","timestamp":1616607855000},"page":"e0249142","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Deficiency in CCR2 increases susceptibility of mice to infection with an intracellular pathogen, Francisella tularensis LVS, but does not impair development of protective immunity"],"prefix":"10.1371","volume":"16","author":[{"given":"Sherry L.","family":"Kurtz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"De Pascalis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anda I.","family":"Meierovics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8779-8657","authenticated-orcid":true,"given":"Karen L.","family":"Elkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"pone.0249142.ref001","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0065-2776(08)60405-8","article-title":"Confrontation between intracellular bacteria and the immune system","volume":"71","author":"UE Schaible","year":"1999","journal-title":"Adv Immunol"},{"issue":"5","key":"pone.0249142.ref002","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a016303","article-title":"The chemokine system in innate immunity","volume":"7","author":"CL Sokol","year":"2015","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"4","key":"pone.0249142.ref003","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1172\/JCI29919","article-title":"Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites","volume":"117","author":"CL Tsou","year":"2007","journal-title":"J. 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