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Mice genetically deficient in IFN-\u03b3-mediated responses (IFNGR2KO mice) and IL-12-mediated responses (Stat4KO mice) were infected with the WA1<jats:italic>Babesia<\/jats:italic>, and observations were made on the course of infection and cytokine responses. Levels of IFN-\u03b3 and IL-12 in serum increased 24 h after parasite inoculation. The augmented susceptibility observed in IFNGR2KO and Stat-4KO mice suggests that the early IL-12- and IFN-\u03b3-mediated responses are involved in protection against acute babesiosis. Resistance appears to correlate with an increase in nitric oxide (NO) production. In order to assess the contribution of different cell subsets to resistance against the parasite, we also studied mice lacking B cells, CD4<jats:sup>+<\/jats:sup>T cells, NK cells, and macrophages. Mice genetically deficient in B lymphocytes or CD4<jats:sup>+<\/jats:sup>T lymphocytes were able to mount protective responses comparable to those of immunosufficient mice. In contrast, in vivo depletion of macrophages or NK cells resulted in elevated susceptibility to the infection. Our observations suggest that a crucial part of the response that protects from the pathogenic<jats:italic>Babesia<\/jats:italic>WA1 is mediated by macrophages and NK cells, probably through early production of IL-12 and IFN-\u03b3, and induction of macrophage-derived effector molecules like NO.<\/jats:p>","DOI":"10.1128\/iai.71.4.2002-2008.2003","type":"journal-article","created":{"date-parts":[[2003,3,24]],"date-time":"2003-03-24T23:07:27Z","timestamp":1048547247000},"page":"2002-2008","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":56,"title":["Resistance to Acute Babesiosis Is Associated with Interleukin-12- and Gamma Interferon-Mediated Responses and Requires Macrophages and Natural Killer Cells"],"prefix":"10.1128","volume":"71","author":[{"given":"Irma","family":"Aguilar-Delfin","sequence":"first","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Wettstein","sequence":"additional","affiliation":[{"name":"Department of Immunology"},{"name":"Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Persing","sequence":"additional","affiliation":[{"name":"Corixa Corporation and Infectious Disease Research Institute, Seattle, Washington 98104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.12.7955-7958.2001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.563"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2478(94)00160-X"},{"key":"e_1_3_2_5_2","first-page":"235","volume":"152","year":"1989","unstructured":"Bancroft, G. 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