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Immunization of susceptible C57BL\/6 mice with CpG ODN deviates the immune response from a Th2\u2010 toward a Th1\u2010type response following infection with <jats:italic>C. neoformans<\/jats:italic>. CpG also induces IL\u201012, TNF, MCP\u20101 and macrophage nitric oxide production. CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T\u2004cells producing IFN\u2010\u03b3 increase in frequency, while those producing IL\u20105 decrease. More importantly, pulmonary eosinophilia is significantly reduced, an effect that depends on IL\u201012 and CD8<jats:sup>+<\/jats:sup> T\u2004cells but not NK cells. CpG treatment also reduces the burden of <jats:italic>C. neoformans<\/jats:italic> in the lung, an effect that is IL\u201012\u2010, NK cell\u2010 and T\u2004cell\u2010independent and probably reflects a direct effect of CpG on pathogen opsonization or an enhancement of macrophage antimicrobial activity. An equivalent beneficial effect is also observed when CpG ODN treatment is delivered during established cryptococcal disease. This is the first study documenting that promotion of lung TLR9 signaling using synthetic agonists enhances host defense. Activation of innate immunity has clear therapeutic potential and may even be beneficial in patients with acquired immune deficiency.<\/jats:p>","DOI":"10.1002\/eji.200425640","type":"journal-article","created":{"date-parts":[[2004,12,14]],"date-time":"2004-12-14T13:46:51Z","timestamp":1103032011000},"page":"273-281","source":"Crossref","is-referenced-by-count":47,"title":["Stimulation via Toll\u2010like receptor 9 reduces <i>Cryptococcus neoformans<\/i>\u2010induced pulmonary inflammation in an IL\u201012\u2010dependent manner"],"prefix":"10.1002","volume":"35","author":[{"given":"Lorna","family":"Edwards","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew\u2004E.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur\u2004M.","family":"Krieg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron\u2004J.","family":"Rae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert\u2004J.","family":"Snelgrove","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Hussell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,12,16]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(99)80025-2"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200204000-00014"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/341564"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(03)00089-4"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198909213211205"},{"issue":"1","key":"e_1_2_7_6_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/mmy.38.1.173.182","article-title":"Epidemiology: surveillance of fungal infections.","volume":"38","author":"Ellis D.","year":"2000","journal-title":"Med. 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