Phagocytosis ofFonsecaea pedrosoiconidia, but not sclerotic cells caused by Langerhans cells, inhibits CD40 and B7-2 expression

Abstract

Fonsecaea pedrosoi is the major etiological agent of chromoblastomycosis, a chronic, suppurative, granulomatous mycosis usually confined to skin and subcutaneous tissues, presenting a worldwide distribution. The host defense mechanisms in chromoblastomycosis have not been extensively investigated. Langerhans cells (LC) are bone-marrow-derived, dendritic antigen-presenting cells of the epidermis, which constitutively express major histocompatibility complex (MHC) class II, and comprise 1-3% of total epidermal cells. LC are localized in suprabasal layers of the epidermis and in mucosa, where they play important roles in skin immune responses. The purpose of the present study was to evaluate the interaction of F. pedrosoi conidia or sclerotic cells with LC purified from BALB/c mice skin. We demonstrate here that LC phagocytose F. pedrosoi conidia but not sclerotic cells in the first 3 h of interaction, inhibiting hyphae formation during 12-hour coculture from both forms, internalized or not. Also, LC maturation, analyzed using CD40 and B7-2 expression, was inhibited by conidia, but not by sclerotic cells, indicating an important innate immunity function of LC against F. pedrosoi infection in these mice.

Fungal x host interactions in Chromoblastomycosis

“…Another important point is that oral immunization results in less footpad inflammation, with the same granulomatous reaction, 26 which corroborates our previous results demonstrating that conidia, but not sclerotic cells, are capable of downregulating costimulatory molecules on Langerhans cells, 25 likely resulting in less inflammation. Interestingly, CD4KO, CD8KO and IL-10KO all presented the same tissue pattern, with a granulomatous reaction and the presence of giant cells, indicating the high capacity of these black fungi to stimulate histiocytes.…”

“…Using this media, we were able to demonstrate that F. pedrosoi conidia, but not sclerotic cells, inhibit CD40 and B7-2 expression in Langerhans cells from Balb/c mice, indicating that the form of the fungus is important for the type of response elicited during the first fungal-cell interactions. 25 Regarding this issue of virulence, Machado et al presented new data employing multiple-site inoculation of F. pedrosoi conidia in different mouse strains, as well as in some knockout mice. 26 They showed an equal increase in footpad volume after inoculation when viable or non-viable fungal cells were inoculated some days earlier into the peritoneum, indicating that delayed-type hypersensitivity (DTH) is involved in lesion maintenance in mice.…”

Black Yeasts and Their Filamentous Relatives: Principles of Pathogenesis and Host Defense

“…Similarly, in vitro studies demonstrated that the expression of MHC-II and CD80 molecules in macrophages was downmodulated in the presence of black yeasts (75). In addition, phagocytosis of black yeast cells or conidia by Langerhans cells inhibited the expression of CD40 and CD86 (96).…”

Chromoblastomycosis

“…Fonsecaea pedrosoi requires a low concentration (0.1 mM; pH 2.5) of Ca 2ϩ to differentiate from mycelia to muriform cells, indicating that the ion concentration may be important in the process of transitioning during CBM (58,171,172). Muriform cells collected from lesional tissues can easily differentiate into hyphae and conidia in vitro or can be maintained as muriform cells under harsh conditions of low pH and nonoptimal nutritional sources in liquid medium (170).…”