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The rat antigen-presenting lectin-like receptor complex influences innate immunity and development of infectious diseases

Genes & Immunity volume 10, pages 227–236 (2009)Cite this article

Abstract

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 β-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.

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Acknowledgements

The project was supported by the Swedish Research Council, the Swedish Rheumatism Association, King Gustav V's 80th Birthday Jubilee Foundation, and the FP6 EU-project AutoCure LSHB-CT-2006-018661.

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Author notes

  1. J C Lorentzen and R A Harris: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Karolinska Institutet, Stockholm, Sweden

    J P Guo & J C Lorentzen

  2. Department of Rheumatology and Inflammation Research, Gothenburg, Sweden

    M Verdrengh & A Tarkowski

  3. Department of Biomedicine, University of Gothenburg, Gothenburg, Sweden

    S Lange & E Jennische

  4. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

    J C Lorentzen

  5. Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden

    R A Harris

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  1. J P Guo
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Correspondence to J C Lorentzen.

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Guo, J., Verdrengh, M., Tarkowski, A. et al. The rat antigen-presenting lectin-like receptor complex influences innate immunity and development of infectious diseases. Genes Immun 10, 227–236 (2009). https://doi.org/10.1038/gene.2009.4

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