Paracoccidioides brasiliensisinteracts with dermal dendritic cells and keratinocytes in human skin and oral mucosa lesions

Abstract

Paracoccidioidomycosis (PCM) is a systemic disease caused by the fungus Paracoccidioides brasiliensis and Paracoccidioides lutzii. In PCM the skin and oral mucosa are often affected. Dendritic cells and keratinocytes of the integument play a role in innate and adaptive immune response against pathogens, due to their function as antigen presenting cells. Aiming to verify the interaction of P. brasiliensis with these cell populations, we studied 52 skin and 47 oral mucosa samples taken from patients with proven diagnosis of PCM. The biopsies were subjected to immunohistochemical and/or immunofluorescence staining with anti-factor XIIIa (marker of dermal dendrocytes), anti-CD207 (marker of mature Langerhans cells), anti-pan cytokeratins (AE1-AE3) and anti-P. brasiliensis antibodies. Analyses with confocal laser microscopy were also performed for better visualization of the interaction between keratinocytes and the fungi. In sum, 42% of oral mucosa samples displayed yeast forms in Factor XIIIa dermal dendrocytes cytoplasm. Langerhans cells in skin and oral mucosa samples did not show yeast cells in their cytoplasm. In sum, 54% of skin and 60% of mucosal samples displayed yeast cells in the cytoplasm of keratinocytes. The parasitism of keratinocytes may represent a possible mechanism of evasion of the fungus to local immune mechanisms. Factor XIIIa dendrocytes and keratinocytes may be acting as antigen-presenting cells to fulfill the probably impaired function of Langerhans cells in skin and oral mucosa of human PCM.

Paracoccidioidomycosis: Current Perspectives from Brazil

“…The structures of the cytoskeletons of pulmonary epithelial cells and keratinocytes and their morphological features, including actin, tubulin and cytokeratin, could be affected by the interactions between the host and Paracoccidioides sp [ 127 , 128 ]. Keratinocyte parasitism may represent a possible mechanism by which fungal cells can evade local immune mechanisms [ 129 ]. Furthermore, cytochalasin D and colchicine treatment have been found to reduce Paracoccidioides sp invasion, indicating the functional involvement of microfilaments and microtubules in this process [ 127 , 130 ].…”

In situ immune response in human dermatophytosis: possible role of Langerhans cells (CD1a+) as a risk factor for dermatophyte infection

“…Langerhans cells (LCs) are a population of DCs whose main function is antigen sampling and presentation in the epidermis 17 . In the dermis, an equivalent DC population, called dermal dendrocytes (DD), are as potent as LCs in antigen presentation and they have been involved in the pathogenesis of different fungal infections as paracoccidioidomycosis and chromoblastomycosis 18,19 . Curiously, LCs recognize the antigen trichophytin 20 and altered LC proliferation was associated to dermatophytosis 21 , hinting a possible role in this infection.…”

Organization of the Skin Immune System and Compartmentalized Immune Responses in Infectious Diseases

“…Although LCs are the main type of immune cells in the epidermis, as already mentioned, keratinocytes can participate in the control of the immune response in the tissue microenvironment (343). They do so by releasing antimicrobial peptides, presenting antigens, or participating in innate or adaptive immunity by releasing cytokines that control the cascade of proteins in the immune response to microorganisms ( Fig.…”

“…They do so by releasing antimicrobial peptides, presenting antigens, or participating in innate or adaptive immunity by releasing cytokines that control the cascade of proteins in the immune response to microorganisms ( Fig. 5) (343). The first cytokine identified as being released by keratinocytes was IL-1.…”