Monocyte-Derived Dendritic Cells from Patients with Dermatophytosis Restrict the Growth of Trichophyton rubrum and Induce CD4-T Cell Activation

Abstract

Dermatophytes are the most common agents of superficial mycoses that are caused by mold fungi. Trichophyton rubrum is the most common pathogen causing dermatophytosis. The immunology of dermatophytosis is currently poorly understood. Recently, our group investigated the interaction of T. rubrum conidia with peritoneal mouse macrophages. We found that macrophages phagocytose T. rubrum conidia resulted in a down-modulation of class II major histocompatibility complex (MHC) antigens and in the expression of co-stimulatory molecules. Furthermore, it induced the production of IL-10, and T. rubrum conidia differentiated into hyphae that grew and killed the macrophages after 8 hrs of culture. This work demonstrated that dendritic cells (DCs) and macrophages, from patients or normal individuals, avidly interact with pathogenic fungus T. rubrum. The dermatophyte has two major receptors on human monocyte-derived DC: DC-SIGN and mannose receptor. In contrast macrophage has only mannose receptor that participates in the phagocytosis or bound process. Another striking aspect of this study is that unlike macrophages that permit rapid growth of T. rubrum, human DC inhibited the growth and induces Th activation. The ability of DC from patients to interact and kill T. rubrum and to present Ags to T cells suggests that DC may play an important role in the host response to T. rubrum infection by coordinating the development of cellular immune response.

Dectin-1 and Dectin-2 promote control of the fungal pathogenTrichophyton rubrumindependently of IL-17 and adaptive immunity in experimental deep dermatophytosis

“…While deficiencies in other PRRs also impair the fungal control and promote the infection-as we and others have previously shown for mannose receptor and DC-SIGN, 41 the NLRP3 inflammasome 17 and DC-HIL 42 -here we stress the great and cooperative contribution of Dectin-1 and Dectin-2 against this pathogen. Collectively, these works indicate that the immunity to T. rubrum is a complex, rather than a straightforward, framework that relies on multiple inputs for appropriate control and where individual interferences may compromise its performance.…”

“…Accordingly, HIV was shown to act directly on macrophages, compromising the signaling pathways of TLRs and Dectin-1. 30 Moreover, while lymphocytes from immunocompetent patients with dermatophytosis can proliferate in response to T. rubrum antigens and still show some fungicidal activity in vitro, 31,32 patient-derived dendritic cells are also able to induce T-cell proliferation, indicating normal antigen presentation and co-stimulatory capabilities, 33 and suggesting that dermatophytosis is not necessarily associated with depressed or altered adaptive immunity. Recently, Baltazar et al showed IL-12 and IFN-g responses are required to combat T. rubrum.…”

Perspective on animal models of dermatophytosis caused byTrichophyton rubrum

“…Santiago et al 18 Biopsy specimens from skin lesions Tissues from localized (LD) and disseminated (DD) dermatophytoses by T. rubrum Reduced TLR4 expression, but not TLR2 expression, was detected in both DD and LD patientscompared with the control group.…”

“…For example, the models have shown that IFN-g, IL-12, IL-1b, and IL-17 are important cytokines for controlling T. rubrum infection and that skin lesions of patients present lower expression of Toll-like receptor 4 (TLR4) than that seen in the control groups. 1,17,8 Furthermore, both dendritic cells (DCs) and macrophages interact with T. rubrum conidia, 8,9,18 but Santiago et al 18 demonstrated that only DCs inhibited T. rubrum growth and induced Th activation, suggesting that these cells play an important role in coordinating the development of the cellular immune response during T. rubrum infection. In conclusion, much work is still required to provide scientific information about dermatophyte infections to a level at least similar to that for other fungal infections caused by species that are easier to manipulate (e.g., Candida and Cryptococcus).…”

Avaliação dos efeitos de antígenos de Paracoccidioides brasiliensis em células dendríticas derivadas de monócitos de pacientes com paracoccidioidomicose: expressão de moléculas de superfície, linfoproliferação e secreção de citocinas

“…Assim, Rissoan et al (1999) (Cambi et al, 2003), Penicillium marneffei (Ngaosuwankul et al, 2008) e Trichophyton rubrum (Santiago et al, 2014).…”