Journal
GENES AND IMMUNITY
Volume 10, Issue 3, Pages 227-236Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gene.2009.4
Keywords
C-type lectin; congenic strain; infection; innate immunity; macrophage; cytokine
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Funding
- Swedish Research Council
- Swedish Rheumatism Association
- King Gustav V's 80th Birthday Jubilee Foundation
- FP6 EU [LSHB-CT-2006-018661]
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Genetic variation in the antigen-presenting lectin-like receptor gene complex (APLEC) associates with autoimmunity and arthritis in rats and humans. We hypothesized that the encoded C-type lectin-like receptors might influence innate immunity and responses to infectious agents. To test this hypothesis, we compared in vivo and in vitro phenotypes in DA rats and APLEC-congenic rats. Survival rates following infection with Staphylococcus aureus and Herpes simplex virus differed significantly between the two strains. Likewise, differential delayed type hypersensitivity (DTH), an immunological reaction involving T lymphocytes and macrophages, was observed in response to provocation with the chemical oxazolone. Unstimulated bone marrow-derived macrophages from the two strains appeared to already have polarized activation states with different mRNA levels of CD163 and Dectin-1 receptors. Following stimulation with a panel of microbial agents, differences in induced mRNA and protein levels were shown for interleukin (IL)-6 and IL-10 following stimulation with lipopolysaccharide, mannan and beta-glucan. Expression levels of APLEC gene mRNAs also differed, and both strains had a notably dichotomous expression of the genes, with general downregulation of all four Dcir genes and upregulation of Mincle and Mcl. We suggest that human APLEC genes may similarly regulate infectious diseases, DTH and general macrophage activation status. Genes and Immunity (2009) 10, 227-236; doi:10.1038/gene.2009.4; published online 12 March 2009
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