RESUMEN
OBJECTIVE: The aim of this study was to investigate the influence of aging on the internalization and the production of nitric oxide (NO) by peritoneal adherent cells (PAC), in response to Candida albicans (C. albicans). MATERIAL AND METHODS: PAC obtained from young and aged mice were challenged with dead or viable C. albicans by using predetermined proportions (cells:yeast) for 30 and 120 minutes. Phagocytosis was analyzed by acridine orange dye, and NO production by the Griess reaction. RESULTS: C. albicans phagocytosis by PAC from aged mice was similar to that of young mice, although the cells from older mice cells present more internalized fungi compared with matched control. In addition, a tendency towards impaired NO production by peritoneal mononuclear phagocytes from aged mice was observed. CONCLUSIONS: PAC from aged mice may capture and store many fungi, which in turn may mean that these cells are effectively unable to eliminate fungi, probably due to impaired NO production. Therefore, considering the important role of C. albicans overgrowth in the pathogenesis of DS and the aspects observed in this study, aging may favor the onset and severity of local candidosis such as DS and its systemic forms.
Asunto(s)
Envejecimiento/fisiología , Candida albicans/patogenicidad , Adhesión Celular/fisiología , Óxido Nítrico/biosíntesis , Fagocitosis/fisiología , Estomatitis Subprotética/metabolismo , Estomatitis Subprotética/microbiología , Factores de Edad , Animales , Candida albicans/aislamiento & purificación , Candidiasis/microbiología , Masculino , Ratones Endogámicos C57BL , Óxido Nítrico/análisis , Peritoneo/citología , Valores de Referencia , Factores de TiempoRESUMEN
Abstract Elderly denture wearers are commonly affected by Candida-associated denture stomatitis (DS), an inflammatory process of the oral mucosa strongly associated with Candida spp and other microorganisms, as well as local and systemic factors. The impaired immune response against pathogens is among the inherent host factors that have been also associated with the pathogenesis of DS. Mononuclear phagocytes respond to the pathogens through phagocytosis followed by the production of several substances inside the phagosomes, among them are the reactive nitrogen species (RNS). A failure in these mechanisms may contribute to the DS development. Objective The aim of this study was to investigate the influence of aging on the internalization and the production of nitric oxide (NO) by peritoneal adherent cells (PAC), in response to Candida albicans (C. albicans). Material and methods PAC obtained from young and aged mice were challenged with dead or viable C. albicans by using predetermined proportions (cells:yeast) for 30 and 120 minutes. Phagocytosis was analyzed by acridine orange dye, and NO production by the Griess reaction. Results C. albicans phagocytosis by PAC from aged mice was similar to that of young mice, although the cells from older mice cells present more internalized fungi compared with matched control. In addition, a tendency towards impaired NO production by peritoneal mononuclear phagocytes from aged mice was observed. Conclusions PAC from aged mice may capture and store many fungi, which in turn may mean that these cells are effectively unable to eliminate fungi, probably due to impaired NO production. Therefore, considering the important role of C. albicans overgrowth in the pathogenesis of DS and the aspects observed in this study, aging may favor the onset and severity of local candidosis such as DS and its systemic forms.
Asunto(s)
Animales , Masculino , Fagocitosis/fisiología , Estomatitis Subprotética/metabolismo , Estomatitis Subprotética/microbiología , Candida albicans/patogenicidad , Envejecimiento/fisiología , Adhesión Celular/fisiología , Óxido Nítrico/biosíntesis , Peritoneo/citología , Valores de Referencia , Factores de Tiempo , Candida albicans/aislamiento & purificación , Candidiasis/microbiología , Factores de Edad , Ratones Endogámicos C57BL , Óxido Nítrico/análisisRESUMEN
Candida-associated denture stomatitis (DS) is the most frequent lesion among denture wearers, especially the elderly. DS is strongly associated with Candida albicans, as well as local and systemic factors, such as impaired immune response. Monocytes are important in the protective immune response against the fungus by the production of cytokines that recruit and activate leukocytes. There are functional changes in these cells with age, and individual alterations involving monocyte response may predispose the host to developing infections by Candida spp. In this study, our aim was to evaluate the production of TNF-α, IL-6, CXCL8, IL-1ß, MCP-1 and IL-10 by monocytes from elderly denture wearers with/without DS and elderly or young non-denture wearers. We detected that monocytes from elderly denture wearers with Candida-related denture stomatitis produced lower levels of CXCL-8, IL-6 and MCP-1. This imbalance in cytokine levels was observed in spontaneous or LPS-stimulated production. Therefore, our data suggested that inherent aspects of the host, such as changes in cytokine production by monocytes, might be associated with the development and the persistence of DS irrespective of aging.
Asunto(s)
Candida/inmunología , Candidiasis/inmunología , Citocinas/inmunología , Mediadores de Inflamación/inmunología , Monocitos/inmunología , Estomatitis Subprotética/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Candida/clasificación , Candida/fisiología , Candida albicans/inmunología , Candida albicans/fisiología , Candida tropicalis/inmunología , Candida tropicalis/fisiología , Candidiasis/metabolismo , Candidiasis/microbiología , Quimiocina CCL2/inmunología , Quimiocina CCL2/metabolismo , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Interacciones Huésped-Patógeno/inmunología , Humanos , Mediadores de Inflamación/metabolismo , Interleucina-6/inmunología , Interleucina-6/metabolismo , Interleucina-8/inmunología , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Monocitos/microbiología , Especificidad de la Especie , Estomatitis Subprotética/metabolismo , Estomatitis Subprotética/microbiologíaRESUMEN
This study evaluated the expression of pattern recognition receptors (PRRs) and activation factors associated with salivary and blood neutrophils from different aged patients diagnosed with Candida-related denture stomatitis (DS). Expression of neutrophil PRRs was determined by flow cytometry and immunofluorescence, and the levels of selected cytokines that influence immune activation were determined by ELISA. The salivary (but not the serum derived) neutrophils of individuals with DS were found to have an increased expression of CD69 regardless of the age of the patient compared to patients without DS. However, these salivary neutrophils had a lower expression of CD66b and CD64. Expression of TLR2 was lower on the salivary- and serum-derived neutrophils from elderly individuals compared to the neutrophils of younger subjects, regardless of whether the individual had DS. Salivary interleukin (IL)-4 was elevated in both of the elderly subject groups (with or without DS). Only elderly DS patients were observed to have increased serum IL-4 levels and reduced salivary IL-12 levels. Younger DS patients showed an increase in salivary IL-10 levels, and both the saliva and the serum levels of IFN-γ were increased in all of the younger subjects. Our data demonstrated that changes in both the oral immune cells and the protein components could be associated with DS. Furthermore, changes in the blood-derived factors were more associated with age than DS status.