The cytotoxic T cells may contribute to the in situ immune response in Jorge Lobo's Disease human lesions.

Jorge Lobo's Disease (JLD) is a cutaneous chronic granulomatous disease caused by the pathogenic fungus Lacazia loboi. It is characterized by a granulomatous reaction with multinucleated giant cells and high number of fungal cells. In order to contribute to the comprehension of immune mechanisms in JLD human lesions, we studied the cytotoxic immune response, focusing on TCD8+ and NK cells, and granzyme B. Forty skin biopsies of lower limbs were selected and an immunohistochemistry protocol was developed to detect CD8+ T cells, NK cells and Granzyme B. In order to compare the cellular populations, we also performed a protocol to visualize TCD4+ cells. Immunolabeled cells were quantified in nine randomized fields in the dermis. Lesions were characterized by inflammatory infiltrate of macrophages, lymphocytes, epithelioid and multinucleated giant cells with intense number of fungal forms. There was a prevalence of CD8 over CD4 cells, followed by NK cells. Our results suggest that in JLD the cytotoxic immune response could represent another important mechanism to control Lacazia loboi infection. We may suggest that, although CD4+ T cells are essential for host defense in JLD, CD8+ T cells could play a role in the elimination of the fungus.

Th17 and regulatory T cells contribute to the in situ immune response in skin lesions of Jorge Lobo's disease.

Jorge Lobo's disease (JLD) is a chronic granulomatous mycosis described in various Latin American countries. The main objective of the present study was to investigate the possible role of Th17 and Foxp3+ Treg cells in the pathogenesis of Jorge Lobo's disease. Human skin biopsies were submitted to an immunohistochemistry protocol to detect Foxp3, interleukin (IL)-1beta, CD25, IL-6, IL-17, and IL-23. The epidermis presented acanthosis, hyperkeratosis, and frequent presence of fungi. The dermis presented inflammatory infiltrate comprising macrophages, lymphocytes, epithelioid and multinucleated cells, and an intense number of fungi. Foxp3+ Treg cells and IL-17+ cells were visualized in lymphocytes in the inflammatory infiltrate. IL-1, IL-2R (CD25), IL-6, and IL-23 were visualized in the dermis, intermingled with fungal cells, permeating or participating of the granuloma. Following IL-17, the most prominent cytokine was IL-6. IL-23 and cells expressing CD25 were present in fewer number. The comparative analysis between IL-17 and Foxp3 demonstrated a statistically significant increased number of IL-17+ cells. Th17 cells play a role in the immune response of JLD. IL-1beta and IL-6 added to the previously described increased number of TGF-beta would stimulate such pattern of response. Th17 cells could be present as an effort to modulate the local immune response; however, high levels of a Th17 profile could overcome the role of Treg cells. The unbalance between Treg/Th17 cells seems to corroborate with the less effective immune response against the fungus.