title: Cross-protective TH1 immunity against Aspergillus fumigatus and Candida albicans.
abstract: T cell-mediated heterologous immunity to different pathogens is promising for the development of immunotherapeutic strategies. Aspergillus fumigatus and Candida albicans, the 2 most common fungal pathogens causing severe infections in immunocompromised patients, are controlled by CD4+ type 1 helper T (T(H)1) cells in humans and mice, making induction of fungus-specific CD4+ T(H)1 immunity an appealing strategy for antifungal therapy. We identified an immunogenic epitope of the A fumigatus cell wall glucanase Crf1 that can be presented by 3 common major histocompatibility complex class II alleles and that induces memory CD4+ T(H)1 cells with a diverse T-cell receptor repertoire that is cross-reactive to C albicans. In BALB/c mice, the Crf1 protein also elicits cross-protection against lethal infection with C albicans that is mediated by the same epitope as in humans. These data illustrate the existence of T cell-based cross-protection for the 2 distantly related clinically relevant fungal pathogens that may foster the development of immunotherapeutic strategies.
authors: Department of Internal Medicine II, Division of Hematology, University of Würzburg, Würzburg, Germany.
authors: Claudia
authors: C
authors: Stuehler
authors: Nina
authors: N
authors: Khanna
authors: Silvia
authors: S
authors: Bozza
authors: Teresa
authors: T
authors: Zelante
authors: Silvia
authors: S
authors: Moretti
authors: Michaela
authors: M
authors: Kruhm
authors: Sarah
authors: S
authors: Lurati
authors: Barbara
authors: B
authors: Conrad
authors: Eike
authors: E
authors: Worschech
authors: Stefan
authors: S
authors: Stevanović
authors: Sven
authors: S
authors: Krappmann
authors: Hermann
authors: H
authors: Einsele
authors: Jean-Paul
authors: JP
authors: Latgé
authors: Juergen
authors: J
authors: Loeffler
authors: Luigina
authors: L
authors: Romani
authors: Max S
authors: MS
authors: Topp
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology* / Q000472:pathogenicity; D015153:Blotting, Western; D002176:Candida albicans / Q000276:immunology* / Q000472:pathogenicity; D002177:Candidiasis / Q000276:immunology* / Q000517:prevention & control*; D049109:Cell Proliferation; D056738:Cross Protection; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006026:Glycoside Hydrolases / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014611:Vaccination
chemical_list: D010446:Peptide Fragments; D012333:RNA, Messenger; D007371:Interferon-gamma; D006026:Glycoside Hydrolases