Dectin-1 and Dectin-2 promote control of the fungal pathogen Trichophyton rubrum independently of IL-17 and adaptive immunity in experimental deep dermatophytosis.
A clarion call for preventing taxonomical errors of dermatophytes using the example of the novel Trichophyton mentagrophytes genotype VIII uniformly isolated in the Indian epidemic of superficial dermatophytosis.
Dectin-1 and Dectin-2 promote control of the fungal pathogen Trichophyton rubrum independently of IL-17 and adaptive immunity in experimental deep dermatophytosis.
Furthermore, we generated and infected IL-17A and IFN-γ double-deficient mice and showed that both fungal clearance and clinical recovery were much lower in these mice than in single-deficient mice, suggesting the complementary roles of the two cytokines in dermatophytosis resolution.
Furthermore, we generated and infected IL-17A and IFN-γ double-deficient mice and showed that both fungal clearance and clinical recovery were much lower in these mice than in single-deficient mice, suggesting the complementary roles of the two cytokines in dermatophytosis resolution.
Here, we uncovered the C-type lectin receptors, Dectin-1 and Dectin-2, as key elements in the immune response to T. rubrum infection in a model of deep dermatophytosis.
In conclusion, these data directly show a dual function of IL-17 cytokines in dermatophytosis by controlling superficial infection and down-modulating a T helper type 1 antifungal response.
Inborn errors of interleukin-17 immunity have recently been shown to underlie chronic mucocutaneous candidiasis (CMC), while inborn errors of caspase recruitment domain-containing protein 9 (CARD9) immunity underlie deep dermatophytosis and invasive candidiasis.
Our case highlights susceptibility to invasive dermatophytosis related to autosomal recessive CARD9 deficiency and illustrates the range of CARD9 mutations to be pursued in immunocompetent patients with unexplained deep dermatophyte infections.
Our data indicate a strong fungistatic effect of <i>C. halicacabum</i> against <i>T. rubrum</i>, suggesting its potential therapeutic efficacy in the treatment of dermatophytoses.Additionally, <i>C. halicacabum</i> compounds, and particularly luteolin and rutin, are all possible Hsp90 interactors, explaining their fungistatic activity.
Recently, CARD9 (caspase recruitment domain-containing protein 9) deficiency has been reported in individuals with deep dermatophytosis previously classified as "immunocompetent".
Thus, our data suggest that TCR-mediated immunity is critical for the optimal control of superficial dermatophytosis and that adaptive immunity is polarized to both Th1 and Th17 responses, with the Th17 antifungal response acting on dermatophyte clearance and the Th1 response being involved in both fungal clearance and Th17-inflammation down-modulation.