{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:48:21Z","timestamp":1789444101037,"version":"build-2803163510"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2005,3,30]],"date-time":"2005-03-30T00:00:00Z","timestamp":1112140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,3,30]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>In the present study, we elucidated the effect of synthetic CpG-containing oligodeoxynucleotides (ODN) on pulmonary and disseminated infection caused by Cryptococcus neoformans. CDF-1 mice were inoculated intratracheally with a highly virulent strain of this pathogen, which resulted in massive bacterial growth in the lung, dissemination to the brain and death. Administration of CpG-ODN promoted the clearance of C. neoformans in the lungs, decreased their dissemination to brain and prolonged the survival of infected mice. These effects correlated well with the enhanced production of interleukin (IL)-12 and interferon (IFN)-\u03b3 and attenuated secretion of IL-4 in bronchoalveolar lavage fluids (BALF) and promoted development of Th1 cells, as indicated by the increased production of IFN-\u03b3 by paratracheal lymph node cells upon restimulation with cryptococcal antigens. The IFN-\u03b3 synthesis in BALF was inhibited by depletion of CD8+\u2003and CD4+ T cells on days 7 and 14 after infection, respectively, but not by depletion of NK and \u03b3\u03b4 T cells. Consistent with these data, intracellular expression of IFN-\u03b3 was detected predominantly in CD8+\u2003and CD4+ T cells in the lung on days 7 and 14, respectively. The protective effect of CpG-ODN, as shown by the prolonged survival, was completely and partially inhibited by depletion of CD4+\u2003or CD8+ T cells, respectively, but not by depletion of other cells. Finally, TNF-\u03b1 was markedly induced by CpG-ODN, and the protective effect of this agent was strongly inhibited by neutralizing anti-TNF-\u03b1 MoAb. Our results indicate that CpG-ODN alters the Th1\u2013Th2 cytokine balance and promotes host resistance against infection with C. neoformans.<\/jats:p>","DOI":"10.1111\/j.1365-2249.2005.02772.x","type":"journal-article","created":{"date-parts":[[2005,3,30]],"date-time":"2005-03-30T10:11:11Z","timestamp":1112177471000},"page":"220-229","source":"Crossref","is-referenced-by-count":26,"title":["CpG oligodeoxynucleotides promote the host protective response against infection with<i>Cryptococcus neoformans<\/i>through induction of interferon-gamma production by CD4+ T cells"],"prefix":"10.1093","volume":"140","author":[{"given":"K","family":"Miyagi","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Division of 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