关键词: C57BL/6J mice CD1 mice Candida albicans IFN-γ fungal sepsis zymosan

Mesh : Animals Animals, Outbred Strains Bacterial Outer Membrane Proteins / immunology CD5 Antigens / administration & dosage Candida albicans / immunology pathogenicity Candidiasis / drug therapy immunology Cytokines / blood Disease Models, Animal Disease Susceptibility / immunology microbiology Interferon-gamma / administration & dosage blood therapeutic use Lipopolysaccharides / toxicity Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mycoses / drug therapy immunology Sepsis / drug therapy immunology microbiology mortality Species Specificity Spleen / cytology drug effects metabolism Teichoic Acids / toxicity Zymosan / toxicity

来  源:   DOI:10.1111/cmi.12995   PDF(Sci-hub)

Abstract:
Individual susceptibility differences to fungal infection following invasive and/or immunosuppressive medical interventions are an important clinical issue. In order to explore immune response-related factors that may be linked to fungal infection susceptibility, we have compared the response of inbred C57BL/6J and outbred CD1 mouse strains to different experimental models of fungal sepsis. The challenge of animals with the zymosan-induced generalised inflammation model revealed poorer survival rates in C57BL/6J, consistent with lower Th1 cytokine interferon (IFN)-γ serum levels, compared with CD1 mice. Likewise, ex vivo exposure of C57BL/6J splenocytes to zymosan but also bacterial lipopolisaccharide or lipoteichoic acid, resulted in lower IFN-γ secretion compared with CD1 mice. C57BL/6J susceptibility could be reverted by rescue infusion of relative low IFN-γ doses (0.2 μg/kg) either alone or in combination with the ß-glucan-binding CD5 protein (0.7 mg/kg) leading to improved post zymosan-induced generalised inflammation survival. Similarly, low survival rates to systemic Candida albicans infection (2.86 × 104  CFU/gr) were ameliorated by low-dose IFN-γ infusion in C57BL/6J but not CD1 mice. Our results highlight the importance of strain choice in experimental fungal infection models and provide a susceptibility rationale for more specific antifungal immunotherapy designs.
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