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New Gene found - Triples risk of recurring Vaginal Candidiasis
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Published: 7 years ago

New Gene found - Triples risk of recurring Vaginal Candidiasis

In contrast, the TLR2 Pro631His polymorphism induced an almost threefold increase in the susceptibility to RVVC. TLR2 is an important PRR for C. albicans recognition, activating innate immune responses both alone and in synergy with DECTIN-1 (Ferwerda et al., 2008). The deficiency of TLR2 influences susceptibility to systemic candidiasis in mice (Netea et al., 2004), but no studies have been performed in vaginal candidiasis models. The in silico analysis using homology modeling and conservation analysis suggests detrimental effects of the mutation on the function of the receptor. This is supported by the study of Etokebe et al. (2010) that the Pro631His polymorphism has a dominant negative effect on the TLR2 signaling in HEK-293T cells. Finally, we studied the functional relevance of this polymorphism in primary cells from individuals bearing the various alleles. Although we were able to assess cytokine production in only two individuals with a mutant TLR2 allele, both of them consistently produced very low amounts of the T-cell derived cytokines IFNγ and IL-17, mediators that are crucial for mucosal antifungal defense (Ferwerda et al., 2009; van de Veerdonk et al., 2011). This observation is supported by the finding of Ben-Ali et al. (2011) who demonstrated that the 631His TLR2 variant leads to reduced NF-κB activation.

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