{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:26:26Z","timestamp":1790126786182,"version":"4.0.1"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R56AI177660-01A1"],"award-info":[{"award-number":["1R56AI177660-01A1"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2025,5,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Babesia microti<\/jats:italic>\n                      is the primary cause of human babesiosis in North America. Despite the emergence of the disease in recent years, the pathogenesis and immune response to\n                      <jats:italic toggle=\"yes\">B. microti<\/jats:italic>\n                      infection remain poorly understood. Studies in laboratory mice have shown a critical role for macrophages in the elimination of parasites and infected red blood cells (iRBCs). Importantly, the underlying mechanisms that activate macrophages are still unknown. Recent evidence identified the release of extracellular vesicles (EVs) from\n                      <jats:italic toggle=\"yes\">Babesia<\/jats:italic>\n                      iRBCs. EVs are spherical particles released from cell membranes under natural or pathological conditions that have been suggested to play roles in host\u2013pathogen interactions among diseases caused by protozoan parasites. The present study examined whether EVs released from cultured\n                      <jats:italic toggle=\"yes\">Babesia<\/jats:italic>\n                      iRBCs could activate macrophages and alter cytokine secretion. An analysis of vesicle size in EV fractions from\n                      <jats:italic toggle=\"yes\">Babesia<\/jats:italic>\n                      iRBCs showed diverse populations in the &lt;100 nm size range compared to EVs from uninfected RBCs. In co-culture experiments, EVs released by\n                      <jats:italic toggle=\"yes\">B. microti<\/jats:italic>\n                      iRBCs appeared to be associated with macrophage membranes and cytoplasm, indicating uptake of these vesicles\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Interestingly, the incubation of macrophages with EVs isolated from\n                      <jats:italic toggle=\"yes\">Babesia<\/jats:italic>\n                      iRBC culture supernatants resulted in the activation of NF-\u03baB and modulation of pro-inflammatory cytokines. These results support a role for\n                      <jats:italic toggle=\"yes\">Babesia<\/jats:italic>\n                      -derived EVs in macrophage activation and provide new insights into the mechanisms involved in the induction of the innate immune response during babesiosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00333-24","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T03:51:04Z","timestamp":1743738664000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["Activation of macrophages by extracellular vesicles derived from\n                    <i>Babesia<\/i>\n                    -infected red blood cells"],"prefix":"10.1128","volume":"93","author":[{"given":"Biniam","family":"Hagos","sequence":"first","affiliation":[{"name":"American Type Culture Collection","place":["Manassas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Brasov","sequence":"additional","affiliation":[{"name":"American Type Culture Collection","place":["Manassas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Branscome","sequence":"additional","affiliation":[{"name":"American Type Culture Collection","place":["Manassas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujatha","family":"Rashid","sequence":"additional","affiliation":[{"name":"American Type Culture Collection","place":["Manassas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Bradford","sequence":"additional","affiliation":[{"name":"American Type Culture Collection","place":["Manassas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Leonelli","sequence":"additional","affiliation":[{"name":"American Type Culture Collection","place":["Manassas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatah","family":"Kashanchi","sequence":"additional","affiliation":[{"name":"School of Systems Biology, George Mason University","place":["Manassas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5028-1400","authenticated-orcid":true,"given":"Choukri","family":"Ben Mamoun","sequence":"additional","affiliation":[{"name":"Section of Infectious Disease, Yale University School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4357-8940","authenticated-orcid":true,"given":"Robert E.","family":"Molestina","sequence":"additional","affiliation":[{"name":"American Type Culture Collection","place":["Manassas, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"Gray EB Niknafs AM Herwaldt BL. 2019. Surveillance for Babesiosis - United States 2017. Annual Summary. https:\/\/www.cdc.gov\/parasites\/babesiosis\/resources\/babesiosis_surveillance_summary_2017b.pdf."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2018.11.007"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2015.02.008"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2009.02429.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00022-10"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003387"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/496891"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.00085"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02128-14"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.1976.tb03759.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00219605"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201900382"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.962944"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000744"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12727"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.04.009"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens9010021"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.40.4.1259-1263.2002"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0020-7519(86)90118-9"},{"key":"e_1_3_2_21_2","first-page":"640","article-title":"Pathology of experimental Babesia microti infection in the Syrian hamster","volume":"37","author":"Cullen JM","year":"1987","unstructured":"Cullen JM, Levine JF. 1987. 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