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Candida albicans phospholipomannan is sensed through toll-like receptors
Thierry Jouault1, Stella Ibata-Ombetta, Osamu Takeuchi
1Laboratoire de Mycologie Fondamentale et Appliquée, Inserm EMI0360, Université de Lille II, Lille, France. tjouault@univ-lille2.fr
Abstract:
Candida albicans is a common, harmless yeast in the human digestive tract that also causes severe systemic fungal infection in hospitalized patients. Its cell-wall surface displays a unique glycolipid called phospholipomannan (PLM). The ability of PLM to stimulate tumor necrosis factor (TNF)-alpha production by J774 mouse cells correlates with the activation of nuclear factor (NF)-kappaB. We examined the involvement of Toll-like receptors (TLRs) in PLM-dependent stimulation. Compared with wild-type cells, which produced large amounts of TNF-alpha after incubation with PLM, the deletion of the TLR4 and TLR6 genes led to a limited alteration of the PLM-induced response. Deletion of the TLR2 gene completely abolished the cell response. Surface expression of PLM is a phylogenic trait of C. albicans, and the recognition of PLM by TLRs, together with the unique pathogenic potential of C. albicans, suggests that this molecule may be a member of the pathogen-associated molecular pattern family.
Insights
Candida albicans phospholipomannan (PLM) triggers immune responses. Toll-like receptor 2 (TLR2) is crucial for this recognition, highlighting PLM as a potential pathogen-associated molecular pattern.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Candida albicans is a commensal yeast that can cause severe infections in immunocompromised individuals.
- The yeast cell surface features phospholipomannan (PLM), a glycolipid implicated in immune stimulation.
- PLM induces tumor necrosis factor-alpha (TNF-alpha) production, linked to nuclear factor-kappaB (NF-kappaB) activation.
Purpose of the Study:
- To investigate the role of Toll-like receptors (TLRs) in mediating the immune response to C. albicans phospholipomannan (PLM).
Main Methods:
- Utilized J774 mouse cells with gene deletions for TLR4, TLR6, and TLR2.
- Incubated these cells with PLM to assess TNF-alpha production.
- Analyzed the impact of TLR gene deletions on PLM-induced immune cell activation.
Main Results:
- Wild-type cells showed significant TNF-alpha production upon PLM stimulation.
- Deletion of TLR4 and TLR6 genes resulted in minor changes in the PLM response.
- Complete abolition of the cellular response was observed in cells lacking the TLR2 gene.
Conclusions:
- Toll-like receptor 2 (TLR2) is essential for recognizing Candida albicans phospholipomannan (PLM).
- PLM recognition by TLRs suggests its role as a pathogen-associated molecular pattern (PAMP).
- This finding contributes to understanding C. albicans pathogenesis and immune evasion strategies.