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: Claudia Stuehler, Nina Khanna, Silvia Bozza, Teresa Zelante, Silvia Moretti, Michaela Kruhm, Sarah Lurati, Barbara Conrad, Eike Worschech, Stefan Stevanović, Sven Krappmann, Hermann Einsele, Jean-Paul Latgé, Juergen Loeffler, Luigina Romani, Max S Topp
• Journal: Blood (Blood) Vol. 117 Issue 22 Pg. 5881-91 (Jun 02 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21441461 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Peptide Fragments
• RNA, Messenger
• Interferon-gamma
• Glycoside Hydrolases

Topics

• Animals
• Aspergillus fumigatus (immunology, pathogenicity)
• Blotting, Western
• Candida albicans (immunology, pathogenicity)
• Candidiasis (immunology, prevention & control)
• Cell Proliferation
• Cross Protection
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Glycoside Hydrolases (immunology)
• Humans
• Immunity, Cellular
• Interferon-gamma (physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Peptide Fragments (immunology)
• RNA, Messenger (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• T-Lymphocytes (immunology)
• Th1 Cells (immunology)
• Vaccination