Abstract
Candida albicans is usually a benign member of the human gut microbiota, but can become pathogenic under certain circumstances, for example in an immunocompromised host. The innate immune system, in particular neutrophils and macrophages, constitutes a crucial first line of defense against fungal invasion, however adaptive immunity may provide long term protection and thus allow vaccination of at risk patients. While TH1 and TH17 cells are important for antifungal responses, the role of B cells and antibodies in protection from C. albicans infection is less well defined. In this study, we show that C. albicans hyphae but not yeast, as well as fungal cell wall components, directly activate B cells via MyD88 signaling triggered by Toll- like receptor 2, leading to increased IgG1 production. While Dectin-1 signals and specific recognition by the B cell receptor are dispensable for B cell activation in this system, TLR2/MyD88 signals cooperate with CD40 signals in promoting B cell activation. Importantly, recognition of C. albicans via MyD88 signaling is also essential for induction of IL-6 secretion by B cells, which promotes TH17 polarization in T-B cell coculture experiments. B cells may thus be activated directly by C. albicans in its invasive form, leading to production of antibodies and T cell help for fungal clearance.
Highlights
Candida albicans is a commensal fungus that colonizes mucosal tissues, being part of the normal microbiota of most healthy individuals
The fungal cell wall preparation Zymosan showed similar effects to C. albicans hyphae in B cell stimulation with anti-CD40+IL-4 (Figures 1A, B), implying that exposure of cell wall components during hyphae formation of C. albicans is capable of direct stimulation of B cells
We show that mouse and human B cells can be directly stimulated by fungal components, C. albicans hyphae and the fungal cell wall preparation Zymosan, and react by enhanced antibody secretion
Summary
Candida albicans is a commensal fungus that colonizes mucosal tissues, being part of the normal microbiota of most healthy individuals This benign commensal can cause severe infections in immunocompromised hosts, being a common cause of nosocomial infections [1, 2]. One characteristic feature of C. albicans that plays a crucial role during its commensal or pathogenic life style is the fact that it can grow in different morphological forms: an ellipsoid shaped yeast form or an elongated filamentous hyphal form [4]. Both morphologies are found during infection and expose different and characteristic cell wall components and proteins on their surfaces. This difference in morphology leads to differential recognition by host cells and has been shown to be critical for host discrimination between commensal and pathogenic cells [7,8,9,10,11,12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
