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Published on: June 19, 2013
Members of the Candida parapsilosis Complex and Candida albicans are Differentially Recognized by Human Peripheral
Eine Estrada-Mata1, María J Navarro-Arias1, Luis A Pérez-García1
1Departamento de Biología, División de Ciencias Naturales y Exactas, Campus Guanajuato, Universidad de Guanajuato Guanajuato, México.
Abstract:
The systemic infections caused by members of the Candida parapsilosis complex are currently associated to high morbility and mortality rates, and are considered as relevant as those caused by Candida albicans. Since the fungal cell wall is the first point of contact with the host cells, here we performed a comparison of this organelle in members of the C. parapsilosis complex, and its relevance during interaction with human peripheral blood mononuclear cells (PBMCs). We found that the wall of the C. parapsilosis complex members is similar in composition, but differs to that from C. albicans, with less mannan content and more β-glucan and porosity levels. Furthermore, lectin-based analysis showed increased chitin and β1,3-glucan exposure at the surface of C. parapsilosis sensu lato when compared to C. albicans. Yeast cells of members of the C. parapsilosis complex stimulated more cytokine production by human PBMCs than C. albicans cells; and this significantly changed upon removal of O-linked mannans, indicating this wall component plays a significant role in cytokine stimulation by C. parapsilosis sensu lato. When inner wall components were exposed on the wall surface, C. parapsilosis sensu stricto and C. metapsilosis, but not C. orthopsilosis, stimulated higher cytokine production. Moreover, we found a strong dependency on β1,3-glucan recognition for the members of the C. parapsilosis complex, but not for live C. albicans cells; whereas TLR4 was required for TNFα production by the three members of the complex, and stimulation of IL-6 by C. orthopsilosis. Mannose receptor had a significant role during TNFα and IL-1β stimulation by members of the complex. Finally, we demonstrated that purified N- and O-mannans from either C. parapsilosis sensu lato or C. albicans are capable to block the recognition of these pathogens by human PBMCs. Together; our results suggest that the innate immune recognition of the members of the C. parapsilosis complex is differential of that reported for C. albicans. In addition, we propose that purified cell wall mannans can be used as antagonist to block specific receptors on innate immune cells.
Insights
The Candida parapsilosis complex fungal cell wall differs from Candida albicans, impacting immune responses. Mannan removal and exposure of inner components alter cytokine production by human immune cells.
Area of Science:
- Mycology and Immunology
- Host-pathogen interactions
- Innate immunity
Background:
- Systemic Candida infections, particularly by the Candida parapsilosis complex, cause significant morbidity and mortality.
- The fungal cell wall is a critical interface for host-pathogen recognition.
- Understanding cell wall differences between Candida species is crucial for deciphering immune responses.
Purpose of the Study:
- To compare the cell wall composition of Candida parapsilosis complex members with Candida albicans.
- To investigate the role of cell wall components in the interaction with human peripheral blood mononuclear cells (PBMCs).
- To elucidate the mechanisms of innate immune recognition of the Candida parapsilosis complex.
Main Methods:
- Comparative analysis of fungal cell wall composition (mannan, β-glucan, chitin, porosity).
- Lectin-based surface exposure analysis.
- Stimulation assays using human PBMCs and Candida yeast cells or purified cell wall components.
- Inhibition assays using purified mannans.
- Analysis of immune receptor involvement (TLR4, Mannose Receptor).
Main Results:
- Candida parapsilosis complex cell walls have less mannan and more β-glucan and porosity than Candida albicans, with increased chitin and β1,3-glucan surface exposure.
- Candida parapsilosis complex stimulated higher cytokine production in PBMCs, significantly influenced by O-linked mannans.
- β1,3-glucan recognition and TLR4 were crucial for immune responses to the Candida parapsilosis complex, while Mannose Receptor mediated TNFα and IL-1β production.
Conclusions:
- Innate immune recognition of the Candida parapsilosis complex is distinct from Candida albicans, driven by specific cell wall components.
- Exposure of inner cell wall components influences cytokine stimulation.
- Purified mannans can act as antagonists to block pathogen recognition by innate immune cells.
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