{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:44:14Z","timestamp":1770835454577,"version":"3.50.1"},"posted":{"date-parts":[[2024,5,10]]},"group-title":"Microbiology","reference-count":75,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,1,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Some arthropod-borne obligate intracellular rickettsiae are among the most virulent human pathogens.\n                  <jats:italic>Rickettsia<\/jats:italic>\n                  species modulate immune (e.g., macrophages; M\u03a6) and non-immune cell (e.g., endothelial cells) responses to create a habitable environment for host colonization. In particular, M\u03a6 play a crucial role in either terminating an infection at an early stage or succumbing to bacterial replication and colonization. However, our understanding on how\n                  <jats:italic>Rickettsia<\/jats:italic>\n                  species invade host cells, including M\u03a6, remain poorly defined. In this study, we describe a mechanism of host invasion by\n                  <jats:italic>Rickettsia<\/jats:italic>\n                  species, involving rickettsial phosphatidylserine (PS), as a ligand, and the CD300f receptor on M\u03a6. Using bone marrow-derived macrophages (BMDM\u03a6) from wild-type (WT) and CD300f\n                  <jats:sup>-\/-<\/jats:sup>\n                  mice, we demonstrated that engulfment of both pathogenic\n                  <jats:italic>R. typhi<\/jats:italic>\n                  (the etiologic agent of murine typhus) and\n                  <jats:italic>R. rickettsii<\/jats:italic>\n                  (the etiologic agent of Rocky Mountain spotted fever) species as well as the non-pathogenic\n                  <jats:italic>R. montanensis<\/jats:italic>\n                  was significantly reduced in CD300f\n                  <jats:sup>-\/-<\/jats:sup>\n                  BMDM\u03a6 as compared to that of WT BMDM\u03a6. Furthermore, our mechanistic analysis suggests bacterial PS as the potential source for the CD300f-mediated rickettsiae engulfment by M\u03a6.\n                  <jats:italic>In vivo<\/jats:italic>\n                  infection studies using WT and CD300f\n                  <jats:sup>-\/-<\/jats:sup>\n                  C57BL\/6J mice showed that CD300f\n                  <jats:sup>-\/-<\/jats:sup>\n                  animals were protected against\n                  <jats:italic>R. typhi<\/jats:italic>\n                  -or\n                  <jats:italic>R. rickettsii<\/jats:italic>\n                  -induced fatal rickettsiosis, which correlated with levels of bacterial burden detected in the spleens of mice. Adoptive transfer studies further revealed that CD300f-expressing M\u03a6 are important mediators to control rickettsiosis\n                  <jats:italic>in vivo<\/jats:italic>\n                  . Collectively, our findings describe a previously unappreciated role for the efferocytic receptor, CD300f, to facilitate engulfment of rickettsiae within the host.\n                <\/jats:p>","DOI":"10.1101\/2024.05.10.593542","type":"posted-content","created":{"date-parts":[[2024,5,11]],"date-time":"2024-05-11T00:20:21Z","timestamp":1715386821000},"source":"Crossref","is-referenced-by-count":1,"title":["Phosphatidylserine-binding receptor, CD300f, on macrophages mediates host invasion of pathogenic and non-pathogenic rickettsiae"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1436-2809","authenticated-orcid":false,"given":"Oliver H.","family":"Voss","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imran","family":"Moin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hodalis","family":"Gaytan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Sadik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saif","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9216-9270","authenticated-orcid":false,"given":"M. Sayeedur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025013123251316000_2024.05.10.593542v2.1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2310.170309"},{"key":"2025013123251316000_2024.05.10.593542v2.2","doi-asserted-by":"publisher","DOI":"10.1093\/jme\/tjw179"},{"key":"2025013123251316000_2024.05.10.593542v2.3","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.16-0197"},{"key":"2025013123251316000_2024.05.10.593542v2.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012800"},{"key":"2025013123251316000_2024.05.10.593542v2.5","doi-asserted-by":"crossref","unstructured":"Voss OH , Rahman MS . 2021. Rickettsia-host interaction: strategies of intracytosolic host colonization. Pathog Dis 79.","DOI":"10.1093\/femspd\/ftab015"},{"key":"2025013123251316000_2024.05.10.593542v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.08.046"},{"key":"2025013123251316000_2024.05.10.593542v2.7","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12068"},{"key":"2025013123251316000_2024.05.10.593542v2.8","doi-asserted-by":"crossref","unstructured":"Sahni A , Patel J , Narra HP , Schroeder CLC , Walker DH , Sahni SK . 2017. Fibroblast growth factor receptor-1 mediates internalization of pathogenic spotted fever rickettsiae into host endothelium. PLoS One 12.","DOI":"10.1371\/journal.pone.0183181"},{"key":"2025013123251316000_2024.05.10.593542v2.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1314400110"},{"key":"2025013123251316000_2024.05.10.593542v2.10","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011811-132445"},{"key":"2025013123251316000_2024.05.10.593542v2.11","doi-asserted-by":"publisher","DOI":"10.4161\/23723548.2014.964625"},{"key":"2025013123251316000_2024.05.10.593542v2.12","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.11"},{"key":"2025013123251316000_2024.05.10.593542v2.13","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201847951"},{"key":"2025013123251316000_2024.05.10.593542v2.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.02.003"},{"key":"2025013123251316000_2024.05.10.593542v2.15","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-435057"},{"key":"2025013123251316000_2024.05.10.593542v2.16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101549"},{"key":"2025013123251316000_2024.05.10.593542v2.17","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4146"},{"key":"2025013123251316000_2024.05.10.593542v2.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.05.005"},{"key":"2025013123251316000_2024.05.10.593542v2.19","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89531"},{"key":"2025013123251316000_2024.05.10.593542v2.20","doi-asserted-by":"crossref","unstructured":"Voss OH , Cobb J , Gaytan H , Rivera D\u00edaz N , Sanchez R , DeTolla L , Rahman MS , Azad AF . 2022. Pathogenic, but Not Nonpathogenic, Rickettsia spp. Evade Inflammasome-Dependent IL-1 Responses To Establish an Intracytosolic Replication Niche. mBio 13.","DOI":"10.1128\/mbio.02918-21"},{"key":"2025013123251316000_2024.05.10.593542v2.21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005115"},{"key":"2025013123251316000_2024.05.10.593542v2.22","doi-asserted-by":"crossref","first-page":"e0279123","DOI":"10.1128\/spectrum.02791-23","article-title":"Autophagy facilitates intracellular survival of pathogenic rickettsiae in macrophages via evasion of autophagosomal maturation and reduction of microbicidal pro-inflammatory IL-1 cytokine responses","volume":"11","year":"2023","journal-title":"Microbiol Spectr"},{"key":"2025013123251316000_2024.05.10.593542v2.23","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.86"},{"key":"2025013123251316000_2024.05.10.593542v2.24","doi-asserted-by":"crossref","unstructured":"Chen B , Zhao Y , Li Z , Pan J , Wu H , Qiu G , Feng C , Wei C . 2020. Immobilization of Phosphatidylserine by Ethanol and Lysozyme on the Cell Surface for Evaluation of Apoptosis-Like Decay in Activated-Sludge Bacteria. Appl Environ Microbiol 86.","DOI":"10.1128\/AEM.00345-20"},{"key":"2025013123251316000_2024.05.10.593542v2.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.04.027"},{"key":"2025013123251316000_2024.05.10.593542v2.26","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.REV120.011473"},{"key":"2025013123251316000_2024.05.10.593542v2.27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0197012"},{"key":"2025013123251316000_2024.05.10.593542v2.28","doi-asserted-by":"crossref","unstructured":"Bechelli J , Vergara L , Smalley C , Buzhdygan TP , Bender S , Zhang W , Liu Y , Popov VL , Wang J , Garg N , Hwang S , Walker DH , Fang R . 2019. Atg5 supports Rickettsia australis infection in macrophages in vitro and in vivo. Infect Immun 87.","DOI":"10.1128\/IAI.00651-18"},{"key":"2025013123251316000_2024.05.10.593542v2.29","first-page":"962","article-title":"Subversion of Host Innate Immunity by Rickettsia australis via a Modified Autophagic Response in Macrophages","volume":"0","year":"2021","journal-title":"Front Immunol"},{"key":"2025013123251316000_2024.05.10.593542v2.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0673-5"},{"key":"2025013123251316000_2024.05.10.593542v2.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-019-0583-6"},{"key":"2025013123251316000_2024.05.10.593542v2.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2016.02.003"},{"key":"2025013123251316000_2024.05.10.593542v2.33","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2112"},{"key":"2025013123251316000_2024.05.10.593542v2.34","doi-asserted-by":"crossref","unstructured":"Noriea NF , Clark TR , Hackstadt T . 2015. Targeted knockout of the Rickettsia rickettsii OmpA surface antigen does not diminish virulence in a mammalian model system. mBio 6.","DOI":"10.1128\/mBio.00323-15"},{"key":"2025013123251316000_2024.05.10.593542v2.35","doi-asserted-by":"crossref","unstructured":"Burke TP , Engstr\u00f6m P , Tran CJ , Langohr IM , Glasner DR , Espinosa DA , Harris E , Welch MD . 2021. Interferon receptor-deficient mice are susceptible to eschar-associated rickettsiosis. Elife 10.","DOI":"10.7554\/eLife.67029"},{"key":"2025013123251316000_2024.05.10.593542v2.36","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00100-10"},{"key":"2025013123251316000_2024.05.10.593542v2.37","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2222-2228.2004"},{"key":"2025013123251316000_2024.05.10.593542v2.38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1911922116"},{"key":"2025013123251316000_2024.05.10.593542v2.39","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20101157"},{"key":"2025013123251316000_2024.05.10.593542v2.40","doi-asserted-by":"crossref","unstructured":"Borgo GM , Burke TP , Tran CJ , Lo NTN , Engstr\u00f6m P , Welch MD . 2022. A patatin-like phospholipase mediates Rickettsia parkeri escape from host membranes. Nat Commun 13.","DOI":"10.1038\/s41467-022-31351-y"},{"key":"2025013123251316000_2024.05.10.593542v2.41","doi-asserted-by":"crossref","unstructured":"Rumfield C , Hyseni I , McBride JW , Walker DH , Fang R . 2020. Activation of ASC inflammasome driven by toll-like receptor 4 contributes to host immunity against rickettsial infection. Infect Immun 88.","DOI":"10.1128\/IAI.00886-19"},{"key":"2025013123251316000_2024.05.10.593542v2.42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0157231"},{"key":"2025013123251316000_2024.05.10.593542v2.43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004935"},{"key":"2025013123251316000_2024.05.10.593542v2.44","doi-asserted-by":"crossref","unstructured":"Moderzynski K , Papp S , Rauch J , Heine L , Kuehl S , Richardt U , Fleischer B , Osterloh A . 2016. CD4+T Cells Are as Protective as CD8+T Cells against Rickettsia typhi Infection by Activating Macrophage Bactericidal Activity. PLoS Negl Trop Dis 10.","DOI":"10.1371\/journal.pntd.0005089"},{"key":"2025013123251316000_2024.05.10.593542v2.45","doi-asserted-by":"crossref","unstructured":"Voss OH , Gillespie JJ , Lehman SS , Rennoll SA , Beier-Sexton M , Rahman MS , Azad AF . 2020. Risk1, a Phosphatidylinositol 3-Kinase Effector, Promotes Rickettsia typhi Intracellular Survival. mBio 11.","DOI":"10.1128\/mBio.00820-20"},{"key":"2025013123251316000_2024.05.10.593542v2.46","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-35699-4"},{"key":"2025013123251316000_2024.05.10.593542v2.47","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00007-07"},{"key":"2025013123251316000_2024.05.10.593542v2.48","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2015.161"},{"key":"2025013123251316000_2024.05.10.593542v2.49","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103845"},{"key":"2025013123251316000_2024.05.10.593542v2.50","doi-asserted-by":"publisher","DOI":"10.1038\/nature06307"},{"key":"2025013123251316000_2024.05.10.593542v2.51","doi-asserted-by":"publisher","DOI":"10.1038\/nature06329"},{"key":"2025013123251316000_2024.05.10.593542v2.52","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01394-13"},{"key":"2025013123251316000_2024.05.10.593542v2.53","doi-asserted-by":"crossref","unstructured":"Winkler HH , Miller ET . 1978. Phospholipid composition of Rickettsia prowazeki grown in chicken embryo yolk sacs. J Bacteriol.","DOI":"10.1128\/jb.136.1.175-178.1978"},{"key":"2025013123251316000_2024.05.10.593542v2.54","doi-asserted-by":"crossref","unstructured":"Tzianabos T , Moss CW , McDade JE . 1981. Fatty acid composition of rickettsiae. J Clin Microbiol.","DOI":"10.1128\/jcm.13.3.603-605.1981"},{"key":"2025013123251316000_2024.05.10.593542v2.55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1921619117"},{"key":"2025013123251316000_2024.05.10.593542v2.56","doi-asserted-by":"crossref","unstructured":"V A, CA B, TP B, DK N, MD W. 2019. A Metabolic Dependency for Host Isoprenoids in the Obligate Intracellular Pathogen Rickettsia parkeri Underlies a Sensitivity to the Statin Class of Host-Targeted Therapeutics. mSphere 4.","DOI":"10.1128\/mSphere.00848-19"},{"key":"2025013123251316000_2024.05.10.593542v2.57","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00859-17"},{"key":"2025013123251316000_2024.05.10.593542v2.58","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400690"},{"key":"2025013123251316000_2024.05.10.593542v2.59","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401527"},{"key":"2025013123251316000_2024.05.10.593542v2.60","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2006.00495.x"},{"key":"2025013123251316000_2024.05.10.593542v2.61","doi-asserted-by":"publisher","DOI":"10.1038\/nature13168"},{"key":"2025013123251316000_2024.05.10.593542v2.62","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4146"},{"key":"2025013123251316000_2024.05.10.593542v2.63","doi-asserted-by":"publisher","DOI":"10.4161\/23723548.2014.964625"},{"key":"2025013123251316000_2024.05.10.593542v2.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.05.005"},{"key":"2025013123251316000_2024.05.10.593542v2.65","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101549"},{"key":"2025013123251316000_2024.05.10.593542v2.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.08.008"},{"key":"2025013123251316000_2024.05.10.593542v2.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-04647-z"},{"key":"2025013123251316000_2024.05.10.593542v2.68","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00793-12"},{"key":"2025013123251316000_2024.05.10.593542v2.69","doi-asserted-by":"crossref","unstructured":"Lehman SS , Noriea NF , Aistleitner K , Clark TR , Dooley CA , Nair V , Kaur SJ , Rahman MS , Gillespie JJ , Azad AF , Hackstadt T . 2018. The rickettsial ankyrin repeat protein 2 is a type IV secreted effector that associates with the endoplasmic reticulum. mBio 9.","DOI":"10.1128\/mBio.00975-18"},{"key":"2025013123251316000_2024.05.10.593542v2.70","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00155-10"},{"key":"2025013123251316000_2024.05.10.593542v2.71","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.6.1750-1755.1996"},{"key":"2025013123251316000_2024.05.10.593542v2.72","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.63.11.4441-4448.1997"},{"key":"2025013123251316000_2024.05.10.593542v2.73","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.2002.01563.x"},{"key":"2025013123251316000_2024.05.10.593542v2.74","doi-asserted-by":"crossref","unstructured":"Rennoll SA , Rennoll-Bankert KE , Guillotte ML , Lehman SS , Driscoll TP , Beier-Sexton M , Sayeedur Rahman M , Gillespie JJ , Azad AF . 2018. The cat flea (Ctenocephalides felis) immune deficiency signaling pathway regulates Rickettsia typhi infection. Infect Immun 86.","DOI":"10.1128\/IAI.00562-17"},{"key":"2025013123251316000_2024.05.10.593542v2.75","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00462.2010"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.05.10.593542","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:25:41Z","timestamp":1768458341000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.05.10.593542"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,10]]},"references-count":75,"URL":"https:\/\/doi.org\/10.1101\/2024.05.10.593542","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1128\/iai.00059-25","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2024,5,10]]},"subtype":"preprint"}}