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

Abstract

BackgroundChromoblastomycosis 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.MethodologyTwenty-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 findingsIL-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/SignificanceThe 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.

Langerhans Cells Express IL-17A in the Epidermis of Chromoblastomycosis Lesions

“…Similar to the results of Bursch et al [12], we previously demonstrated that CBM lesions display low expression of TGF-β [8], which could reinforce the hypothesis that CD207-positive dermal cells are a new subpopulation of distinct dendritic cells and that, at least in our study, they seem to cooperate with the cascade of the Th17 immune response [12,14]. …”

“…Previously we demonstrated that in CBM lesions a predominance of Th17 cells over Treg cells occurs [8]. The imbalance between the regulator and effector profiles could be a major contributor to the inefficiency of the immune response established in this mycosis.…”

“…These cells could represent an attempt to help the primary immune profile against the fungi. However, it is possible that the marked imbalance between the effectors and regulatory profiles contribute to the ineffective response against verrucous CBM [8]. …”

“…Interestingly, dendritic IL-17+ cells have been observed in the epidermis and dermal infiltrate in human CBM verrucous lesions [8]. In order to verify whether these IL-17+-expressing dendritic cells are in fact LCs, we studied CD207 and IL-17 coexpression by double immunolabeling CBM lesions.…”

Avaliação imuno-histoquímica de elementos da resposta imune e metaloproteinases em lesões cutâneas verrucosas na cromoblastomicose

“…Embora células T reguladoras tenham sido identificadas outrora no microambiente das lesões verrucosas de CBM, nota-se que sua presença e/ou desempenho não são suficientemente capazes de modular a resposta imune de maneira a atingir efetividade ideal para a eliminação do fungo e contenção da doença 26 , o que nos permite explanar no momento sobre as células CD207/IL-17 + se tratarem de outro subtipo de células dendríticas que apesar de guardar semelhanças, não são Langerhans.…”