Morphofunctional evaluation of thymus in hyperglycemic-hypoinsulinemic mice during dermatophytic infection

Abstract

Many works have shown that the enhanced susceptibility to infection seen in diabetic patients can be related to the hyperglycemia-hypoinsulinemia (HH) observed in this condition. Herein, we evaluated the HH effects on the morphofunctional features of the thymus as well as on dermatophytic infection. We demonstrated that, not only the HH condition but also the dermatophytic infection induced transitory alterations in the thymus; it was characterized by loss of cortical-medullar definition and disorganization of the extracellular matrix. These mice also showed a decrease of CD4 1 CD81 thymocytes and a higher percentage of CD4 1 CD8 1 lymphocytes in the peripheral blood. After 7 days, the thymus and peripheral lymphocytes subsets returned to normal values. Interestingly, when the two conditions, HH condition and the infection, were associated, the mice showed a decrease in the percentage of CD4 1 CD8À blood lymphocytes that are involved in the modulation of immune response and have direct cytotoxic effects on the fungus. Taken together, our results showed that both conditions transitorily changed the thymus, but only when both these conditions are present do they trigger persistent changes that might be responsible for the higher susceptibility to dermatophytosis seen in HH patients.

Dermatophyte–host relationship of a murine model of experimental invasive dermatophytosis

“…During this period, the mice assembled a Th1-type immune response and IL-10-mediated immune regulation. Our lab has initiated studies using this experimental model to evaluate dermatophytic infection during a hypoinsulinemia-hyperglycemic (HH) state, a model for diabetes, as this metabolic disease is associated with a high incidence of dermatophytic infection [36]. We report that HH mice exhibited disseminated dermatophytosis following a delay in the infection outcome and that this dermatophytosis was associated with a lower percentage of peripheral blood CD4 þ T cells [36].…”

“…Our lab has initiated studies using this experimental model to evaluate dermatophytic infection during a hypoinsulinemia-hyperglycemic (HH) state, a model for diabetes, as this metabolic disease is associated with a high incidence of dermatophytic infection [36]. We report that HH mice exhibited disseminated dermatophytosis following a delay in the infection outcome and that this dermatophytosis was associated with a lower percentage of peripheral blood CD4 þ T cells [36]. The data obtained from our experimental model may provide more information regarding immunological mechanisms to help researchers better understand the immunological and pathological aspects of invasive dermatophytosis.…”

TLR2−/− Mice Display Increased Clearance of Dermatophyte Trichophyton mentagrophytes in the Setting of Hyperglycemia

“…To evaluate the immune response in a less resistant host, we employed alloxan-induced HH Swiss mice infected with Tm, as previously described (Venturini et al, 2011). We first evaluated the relevance of TLR2 in this context and, subsequently, its impact on the development of infectious processes and induction of the inflammatory response.…”

“…After 14 days, the fungal load decreases and a typical Th1 response is organized, characterized by a positive delayed-type hypersensitivity test and a granulomatous tissue reaction involving epithelioid cells (Venturini et al, 2012). Furthermore, we have employed alloxan-induced hypoinsulinemic-hyperglycemic (HH) mice (Venturini et al, 2011; Fraga-Silva et al, 2015) to evaluate the immune response in a susceptible host, since patients with diabetes mellitus exhibit a higher incidence of dermatophytosis and the disease is usually more severe (Eckhard et al, 2007; Kim et al, 2016). Delayed fungal clearance is observed in HH-infected mice (Venturini et al, 2011).…”

“…Furthermore, we have employed alloxan-induced hypoinsulinemic-hyperglycemic (HH) mice (Venturini et al, 2011; Fraga-Silva et al, 2015) to evaluate the immune response in a susceptible host, since patients with diabetes mellitus exhibit a higher incidence of dermatophytosis and the disease is usually more severe (Eckhard et al, 2007; Kim et al, 2016). Delayed fungal clearance is observed in HH-infected mice (Venturini et al, 2011). In the present study, we investigated the role of TLR2 during the development of Tm infection in naïve and HH mice to better understand the initial events in deep dermatophytosis.…”