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We now show that B6 mice are also more susceptible to<jats:italic>C. immitis<\/jats:italic>pneumonia and that interleukin-10 (IL-10)-deficient (IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>) B6 mice are more resistant to<jats:italic>C. immitis<\/jats:italic>pneumonia. In addition, we established that high levels of IL-10 are sufficient to make genetically resistant mice susceptible to both<jats:italic>C. immitis<\/jats:italic>peritonitis and pneumonia by infecting h.IL-10 transgenic mice. Infected h.IL-10 transgenic mice express lower levels of gamma interferon, IL-12 p40, and inducible nitric oxide synthetase 2 (NOS2) mRNA in their lungs, implicating inducible NOS as a defense mechanism in this disease. We treated DBA\/2 mice with aminoguanidine, and they became more susceptible to<jats:italic>C. immitis<\/jats:italic>peritonitis and pneumonia. We conclude that high levels of IL-10 are both necessary and sufficient to make mice susceptible to<jats:italic>C. immitis<\/jats:italic>, regardless of the genetic background of the mice, and that IL-10 impairs resistance to<jats:italic>C. immitis<\/jats:italic>in part by suppressing NO synthesis.<\/jats:p>","DOI":"10.1128\/iai.01985-05","type":"journal-article","created":{"date-parts":[[2006,5,19]],"date-time":"2006-05-19T23:52:41Z","timestamp":1148082761000},"page":"3387-3395","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":38,"title":["High Levels of Interleukin-10 Impair Resistance to Pulmonary Coccidioidomycosis in Mice in Part through Control of Nitric Oxide Synthase 2 Expression"],"prefix":"10.1128","volume":"74","author":[{"given":"Maria del Pilar","family":"Jimenez","sequence":"first","affiliation":[{"name":"VA Healthcare System"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorraine","family":"Walls","sequence":"additional","affiliation":[{"name":"VA Healthcare System"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Fierer","sequence":"additional","affiliation":[{"name":"VA Healthcare System"},{"name":"Departments of Medicine and Pathology, University of California San Diego School of Medicine, San Diego, California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.1.399"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)00052-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.3.1089-1100.1994"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9918"},{"key":"e_1_3_2_6_2","first-page":"281","year":"1999","unstructured":"Chan, J., and J. 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