Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
1994-4-29
pubmed:abstractText
In contrast to several inbred strains of mice that develop Th1-associated anticandidal protection, DBA/2 mice are highly susceptible to systemic infection with Candida albicans cells of the attenuated variant PCA-2, and fatal outcome is observed in concurrence with sustained CD4+ cell production in vitro of IL-4 and IL-10. These Th2 cytokines were previously shown to inhibit nitric oxide (NO) production and yeast killing by activated macrophage cultures. We now show that macrophages from DBA/2 mice, either intact or infected with PCA-2, have lower capacity than resistant strains to synthesize NO in response to IFN-gamma. However, when treated with anti-IL-10 Abs at the time of infection, DBA/2 mice survived challenge and displayed increased production of NO in vitro after IFN-gamma activation. Cure was associated with the onset of footpad responses and durable protection, and higher frequencies of IFN-gamma-secreting cells were found in splenic CD4+ lymphocytes that expressed lower levels of IL-4 and IL-10 mRNA. Therefore, in DBA/2 mice, IL-10 contributes significantly to the selection of a Th2 response and lethality after PCA-2 challenge. An IL-10-induced defect in the activation and/or expansion of IFN-gamma-producing Th1 cells, IL-10 suppression of yeast killing, and the relative inability of DBA/2 macrophages to produce adequate levels of candidacidal NO may all contribute to the abnormal susceptibility of these mice to candidiasis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
152
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3514-21
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:7908304-Animals, pubmed-meshheading:7908304-Base Sequence, pubmed-meshheading:7908304-CD4-Positive T-Lymphocytes, pubmed-meshheading:7908304-Candidiasis, pubmed-meshheading:7908304-Cytotoxicity, Immunologic, pubmed-meshheading:7908304-DNA Primers, pubmed-meshheading:7908304-Female, pubmed-meshheading:7908304-Gene Expression, pubmed-meshheading:7908304-Hypersensitivity, Delayed, pubmed-meshheading:7908304-Immunity, Cellular, pubmed-meshheading:7908304-Interferon-gamma, pubmed-meshheading:7908304-Interleukin-10, pubmed-meshheading:7908304-Interleukin-4, pubmed-meshheading:7908304-Macrophages, pubmed-meshheading:7908304-Male, pubmed-meshheading:7908304-Mice, pubmed-meshheading:7908304-Mice, Inbred BALB C, pubmed-meshheading:7908304-Mice, Inbred C57BL, pubmed-meshheading:7908304-Mice, Inbred DBA, pubmed-meshheading:7908304-Molecular Sequence Data, pubmed-meshheading:7908304-Nitric Oxide, pubmed-meshheading:7908304-RNA, Messenger
pubmed:year
1994
pubmed:articleTitle
Neutralization of IL-10 up-regulates nitric oxide production and protects susceptible mice from challenge with Candida albicans.
pubmed:affiliation
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't