Journal Article

CD47 Promotes Protective Innate and Adaptive Immunity in a Mouse Model of Disseminated Candidiasis

Stein, Erica V., Navarathna, Dhammika H. M. L. P., Martin-Manso, Gema, Roberts, David D., Lessey-Morillon, Elizabeth C., Nayak, Debasis

2015

Overview

CD47 is a widely expressed receptor that regulates immunity by engaging its counter-receptor SIRPα on phagocytes and its secreted ligand thrombospondin-1. Mice lacking CD47 can exhibit enhanced or impaired host responses to bacterial pathogens, but its role in fungal immunity has not been examined. cd47-/- mice on a C57BL/6 background showed significantly increased morbidity and mortality following Candida albicans infection when compared with wild-type mice. Despite normal fungal colonization at earlier times, cd47-/- mice at four days post-infection had increased colonization of brain and kidneys accompanied by stronger inflammatory reactions. Neutrophil and macrophage numbers were significantly elevated in kidneys and neutrophils in the brains of infected cd47-/- mice. However, no defect in phagocytic activity towards C. albicans was observed in cd47-/- bone-marrow-derived macrophages, and neutrophil and macrophage killing of C. albicans was not impaired. CD47-deficiency did not alter the early humoral immune response to C. albicans. Th1, Th2, and Th17 population of CD4+ T cells were expanded in the spleen, and gene expression profiles of spleen and kidney showed stronger pro-inflammatory signaling in infected cd47-/- mice. The chemoattractant chemokines MIP-2α and MIP-2β were highly expressed in infected spleens of cd47-/- mice. G-CSF, GM-CSF, and the inflammasome component NLRP3 were more highly expressed in infected cd47-/- kidneys than in infected wild-type controls. Circulating pro- (TNF-α, IL-6) and anti-inflammatory cytokines (IL-10) were significantly elevated, but IL-17 was decreased. These data indicate that CD47 plays protective roles against disseminated candidiasis and alters pro-inflammatory and immunosuppressive pathways known to regulate innate and T cell immunity.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adaptive immunity / Animals / Bacteria / Bacterial infections / Bone marrow / Brain / Cancer / Candida albicans / Candida albicans - immunology / Candidiasis / Candidiasis - genetics / Candidiasis - immunology / CD4 antigen / CD47 Antigen - genetics / CD47 Antigen - immunology / Cerebrospinal fluid / Chemokines / Colonization / Comparative analysis / Cytokines / Cytokines - immunology / Defects / Dendritic cells / Development and progression / Disease Models, Animal / Drug resistance / E coli / Fungal infections / Fungi / Gene expression / Glycoproteins / Granulocyte colony-stimulating factor / Granulocyte-macrophage colony-stimulating factor / Health aspects / Helper cells / Immune response / Immune response (humoral) / Immune system / Immunity / Immunity, Cellular / Immunity, Innate / Immunology / Immunosuppression / Immunotherapy / Infections / Inflammasomes / Inflammation / Interleukin 10 / Interleukin 17 / Interleukin 6 / Kidney - immunology / Kidneys / Kinases / Laboratories / Leukocytes (neutrophilic) / Lymphocytes / Lymphocytes T / Macrophages / Macrophages - immunology / Medical research / Mice / Mice, Knockout / Morbidity / Neutrophils / Neutrophils - immunology / Nosocomial infections / Pathogenesis / Pathogens / Pathology / Phagocytes / Physiological aspects / Proteins / Receptors / Recruitment / Rodents / Signal transduction / Signaling / Spleen / T cells / T-Lymphocytes, Helper-Inducer - immunology / Thrombospondin / Tumor necrosis factor