title: Cutting edge: Failure of antigen-specific CD4+ T cell recruitment to the kidney during systemic candidiasis.
abstract: Candida albicans is the leading cause of systemic candidiasis, a fungal disease associated with high mortality and poor treatment options. The kidney is the target organ during infection and whose control is largely dependent on innate immunity, because lymphocytes appear redundant for protection. In this article, we show that this apparent redundancy stems from a failure of Ag-specific CD4(+) T cells to migrate into infected kidneys. In contrast, Ag-specific CD8(+) T cells are recruited normally. Using Ag-loaded immunoliposomes to artificially reverse this defective migration, we show that recruited Ag-specific CD4(+) T cells polarize toward a Th17 phenotype in the kidney and are protective during fungal infection. Therefore, our data explain the redundancy of CD4(+) T cells for defense against systemic infection with C. albicans and have important implications for our understanding of antifungal immunity and the control of renal infections.
authors.affiliation: Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom;
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Drummond
authors.affiliation: Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom;
authors.forename: Carol
authors.initials: C
authors.lastname: Wallace
authors.affiliation: Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom;
authors.forename: Delyth M
authors.initials: DM
authors.lastname: Reid
authors.affiliation: Division of Infectious Diseases, Cincinnati Children's Hospital, Cincinnati, OH 45229; and.
authors.forename: Sing Sing
authors.initials: SS
authors.lastname: Way
authors.affiliation: Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Kaplan
authors.affiliation: Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom; gordon.brown@abdn.ac.uk.
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D019610:Cytoprotection; D005260:Female; D007113:Immunity, Innate; D007668:Kidney / Q000276:immunology* / Q000382:microbiology; D008081:Liposomes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology
chemical_list: D000941:Antigens; D008081:Liposomes; D011948:Receptors, Antigen, T-Cell