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Exposure to host or fungal PGE(2) abrogates protection following immunization with Candida-pulsed dendritic cells.
MedLine Citation:
PMID:  21077736     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Candida albicans produces an immunomodulatory oxylipin from arachidonic acid that is structurally identical to host prostaglandin E(2) (PGE(2)). In terms of host immune responses, PGE(2) can promote Th2 responses, which are non-protective against fungal infections. We investigated the effect of host or fungal PGE(2) on murine bone marrow-derived dendritic cell (DC) cytokine production, and the ability to immunize mice against systemic infection with C. albicans. We used GM-CSF to produce myeloid DCs (GM-DCs) and FLT-3L to enrich for plasmacytoid DCs (FL-DCs). In the presence of hyphae, PGE(2) promoted Th2 cytokine production and suppressed Th1 cytokine production. Immunization with yeast-pulsed DCs but not hyphae-pulsed DCs lead to a reduction in kidney fungal burden during systemic infection, which was most dramatic with FL-DCs. However, exposure to either host or fungal PGE(2) during antigenic stimulation abrogated the ability of yeast-pulsed DCs to protect against infection. The lack of protection was associated with a trend towards reduced Th1 cytokines and increased Th2 cytokines in the spleen. However, the pattern of protection did not completely match cytokine expression. Locally, in FL-DC pulsed mice, reduced Th1 and exacerbated Th2 and Th17 cytokines were only detected in the kidneys of mice that did not show reductions in fungal burden after vaccination. This indicates that host or fungal PGE(2) can shift adaptive responses in favor of the pathogen and that uncontrolled Th17 responses are detrimental during systemic infection.
Authors:
Gitanjali Kundu; Mairi C Noverr
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Publication Detail:
Type:  Journal Article     Date:  2010-11-15
Journal Detail:
Title:  Medical mycology : official publication of the International Society for Human and Animal Mycology     Volume:  49     ISSN:  1460-2709     ISO Abbreviation:  Med. Mycol.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815835     Medline TA:  Med Mycol     Country:  England    
Other Details:
Languages:  eng     Pagination:  380-94     Citation Subset:  IM    
Affiliation:
*Department of Immunology & Microbiology, Wayne State University School of Medicine, Detroit, Michigan.
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