{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:40:32Z","timestamp":1787942432965,"version":"build-2784847793"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>During adaptive immunity to pathogens, dendritic cells (DCs) capture, kill, process, and present microbial Ags to T cells. Ag presentation is accompanied by DC maturation driven by appropriate costimulatory signals. However, current understanding of the intricate regulation of these processes remains limited. Cryptococcus gattii, an emerging fungal pathogen in the Pacific Northwest of Canada and the United States, fails to stimulate an effective immune response in otherwise healthy hosts leading to morbidity or death. Because immunity to fungal pathogens requires intact cell-mediated immunity initiated by DCs, we asked whether C. gattii causes dysregulation of DC functions. C. gattii was efficiently bound and internalized by human monocyte-derived DCs, trafficked to late phagolysosomes, and killed. Yet, even with this degree of DC activation, the organism evaded pathways leading to DC maturation. Despite the ability to recognize and kill C. gattii, immature DCs failed to mature; there was no increased expression of MHC class II, CD86, CD83, CD80, and CCR7, or decrease of CD11c and CD32, which resulted in suboptimal T cell responses. Remarkably, no increase in TNF-\u03b1 was observed in the presence of C. gattii. However, addition of recombinant TNF-\u03b1 or stimulation that led to TNF-\u03b1 production restored DC maturation and restored T cell responses. Thus, despite early killing, C. gattii evades DC maturation, providing a potential explanation for its ability to infect immunocompetent individuals. We have also established that DCs retain the ability to recognize and kill C. gattii without triggering TNF-\u03b1, suggesting independent or divergent activation pathways among essential DC functions.<\/jats:p>","DOI":"10.4049\/jimmunol.1202707","type":"journal-article","created":{"date-parts":[[2013,6,6]],"date-time":"2013-06-06T04:58:04Z","timestamp":1370494684000},"page":"249-261","source":"Crossref","is-referenced-by-count":52,"title":["<i>Cryptococcus gattii<\/i> Is Killed by Dendritic Cells, but Evades Adaptive Immunity by Failing To Induce Dendritic Cell Maturation"],"prefix":"10.1093","volume":"191","author":[{"given":"Shaunna M","family":"Huston","sequence":"first","affiliation":[{"name":"Department of Microbiology and Infectious Disease, University of Calgary , Calgary, Alberta, T2N 4N1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu Shun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Disease, University of Calgary , Calgary, Alberta, T2N 4N1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danuta","family":"Stack","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Disease, University of Calgary , Calgary, Alberta, T2N 4N1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Timm-McCann","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Disease, University of Calgary , Calgary, Alberta, T2N 4N1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth J","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Disease, University of Calgary , Calgary, Alberta, T2N 4N1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anowara","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Disease, University of Calgary , Calgary, Alberta, T2N 4N1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byron M","family":"Berenger","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Disease, University of Calgary , Calgary, Alberta, T2N 4N1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard F","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Infectious Disease, University of Calgary , Calgary, Alberta, T2N 4N1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pina","family":"Colarusso","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Calgary , Calgary, Alberta, T2N 4N1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H","family":"Mody","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Calgary , Calgary, Alberta, T2N 4N1","place":["Canada"]},{"name":"Department of Internal Medicine, University of Calgary , Calgary, Alberta, T2N 4N1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,7,1]]},"reference":[{"key":"2025032405025963000_r1","doi-asserted-by":"crossref","first-page":"5132","DOI":"10.1073\/pnas.75.10.5132","article-title":"Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice","volume":"75","author":"Steinman","year":"1978","journal-title":"Proc. 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