In Situ Immune Response in Human Chromoblastomycosis – A Possible Role for Regulatory and Th17 T Cells.

Background: Chromoblastomycosis is a chronic fungal infection that affects skin and subcutaneous tissue. Lesions can be classified in tumorous, verrucous, cicatricial and plaque type. The cellular immune response in the severe form of the disease seems to correlate with a Th2 pattern of cytokines. The humoral immune response also seems to play a role. We intended to explore the populations of regulatory T cells and the Th17 pattern. Methodology: Twenty-three biopsies of verrucous form were obtained from patients with clinical, culture and histopathological diagnostic of chromoblastomycosis, without treatment. It was performed an immunohistochemistry method to detect Foxp3, CD25, TGF-β, IL-6, IL-17 and IL-23. Principal findings: IL-17 was the only cytokine with high expression in CBM when compared to normal skin. The expression of Treg cells, TGF- β, IL-6 and IL-23 were similar to normal skin. Conclusions/Significance: The constitution of a local immune response with high expression of IL-17 and low expression of other cytokines could be at least in part, an attempt to help the immune system against fungal infection. On the other hand, high levels of local immune response mediated by Th17 profile could overcome the role of Treg cells. The inefficient immunomodulation as a consequence of the unbalance by Treg/Th17 cells seems to corroborate with the less effective immune response against fungi. Author Summary: Chromoblastomycosis (CBM) is a chronic infection that affects skin and subcutaneous tissue, caused by some fungi which have a brownish color due to the presence of melanin pigments. The most frequent lesions are of verrucous type. Here we describe the participation of regulatory T cells and cells with the Th17 pattern of cytokines. High levels of Th17 cells participate in chronic inflammatory conditions, once at least in part they could improve the immune response and act in concomitance to the Th1 and Th2 patterns. Our results indicate a predominance of the Th17 pattern over Treg cells in verrucous lesions. We speculate that the local immune imbalance in CBM lesions characterized by exacerbated Th17 response, probably by suppressing the Treg response, is not effective for total fungal elimination. Even after long-period treatments, most patients has no absolute cure and often there is recurrence of the lesions. We believe that our study could contribute to the understanding of the immunopathogenesis of CBM and in such a way, presents some aspects to new possible therapies. [ABSTRACT FROM AUTHOR]