Participación del polimorfonuclear neutrófilo en la respuesta inmune contra Paracoccidioides brasiliensis

Abstract

~o@oración para lnvestigaciones ~ibló~icas, Medellín, ~olombii. Vscuela de Bacteriología y Laboratorio Clínico, Universidad de Antioquia, Medellín, Colombia La paracoccidioidomicosis, micosis profunda de gran importancia en Latinoamérica, se caracteriza por presentar una respuesta inflamatoria aguda en el pulmón, órgano blanco del proceso infeccioso. En las etapas iniciales, esta respuesta se caracteriza principalmente por un infiltrado de polimorfonucleares neutrófilos (PMN), los que, de acuerdo con estudios histopatológicos y de lavados broncoalveolares, representan más del 85% de las células allí presentes. Las evidencias presentadas en esta revisión sugieren que el PMN participa activamente en la respuesta inflamatoria aguda inducida por Paracoccidioides brasiliensis, como lo demuestra la inhibición de su crecimiento después de su interacción con tales PMN. Igualmente, se conoce que algunas etapas del mecanismo fungicida exhibido por esta célula fagocítica están mediadas por los reactivos intermediarios del oxígeno, así como también por el efecto activador de algunas citocinas como IFN y, GM-CSF e IL-lb. En efecto, fracciones o componentes del hongo inducen la migración al sitio inflamatorio y la activación de los PMN, evidenciada por el aumento en los productos del estallido respiratorio.Palabras clave: polimorfonuclear neutrófilo, Paracoccidioides brasiliensis, paracoccidioidomicosis, estallido respiratorio, respuesta inflamatoria. Polymorphonuclear neutrophil participation in immune response t o Paraccocidioides brasiliensisParacoccidioidomycosis, a systemic mycosis of great importance in Latin America, is histologically characterized by an acute inflammatoty response in the lung target organ. During the early stages of infection, tissue response is mainly characterized by the presence of polymorphonuclear neutrophils (PMN) which represent over 85% of al1 cells (demonstrated by histopathology and bronchoalveolar lavage). Evidence is presented herein that PMNs actively participate during the acute inflammatory response induced by Paracoccidioides brasiliensis. This is shown by growth inhibition following the interaction of the fungus with these phagocytic cells. Certain of the killing mechanisms exhibited by this phagocytic cell are mediated by the reactive oxygen intermediates, as well as by the activating mechanisms exerted by certain cytokines (IFN-y, GM-CSF and IL-1 P). Furthermore, fungal fractions or components are capable of inducing both activation of PMN and migration to the inflammatory site as revealed by the increase of the products resulting from the respiratoty burst.

Depletion of Neutrophils Promotes the Resolution of Pulmonary Inflammation and Fibrosis in Mice Infected with Paracoccidioides brasiliensis

“…Several studies have been highlighting the importance of neutrophils in the pathogenesis of PCM, most of them dedicated to evaluate the role of these cells during early stages of infection and their influence on the adaptive immune response [ 8 , 11 , 12 ]. However, to our knowledge, there are no studies focused on evaluating neutrophil involvement in the chronic stages or in the development of fibrosis observed in this mycosis.…”

“…Multiple studies have demonstrated the relevance of neutrophils in the pathogenesis of PCM, especially during the early stages of infection [ 7 , 8 ]. Recently, it has been suggested that neutrophils may modulate the innate and adaptive immune response against P .…”

The Therapy of Pulmonary Fibrosis in Paracoccidioidomycosis: What Are the New Experimental Approaches?

“…Regarding PF due to P. brasiliensis infection, a strategy using a mAb specific to neutrophils was employed [10,11]. It has been described that neutrophils play an important role in the pathogenesis of PCM; thus, these phagocytic cells exert a protecting effect during the early stages of infection [66], as well as being relevant during the chronic stage of the mycosis as they are present in high numbers accompanying the granulomatous lesions [8,23,67]. With this in mind, P. brasiliensis-infected mice were treated with a mAb specific to neutrophils at four weeks post-infection (when the fibrotic process begins) followed by doses every two days for two weeks.…”

The Role of the Interleukin-17 Axis and Neutrophils in the Pathogenesis of Endemic and Systemic Mycoses

“…Similarly, it has been suggested that neutrophils are essential during the acute inflammatory phase since they represent more than 85% of inflammatory cells and could positively modulate the innate immune response through the production of proinflammatory cytokines and lipidic mediators in the infected lung tissue (Gonzalez and Cano, 2001;Gonzalez et al, 2003;Balderramas et al, 2014). Along these lines, using an experimental model of pulmonary PCM in mice with intermediate susceptibility to infection and treated with a monoclonal antibody specific to neutrophils, we reported that compared to control mice, infected and neutrophil-depleted mice showed decreased survival rates during the early stage of infection, accompanied by an increase in both the fungal burden and the inflammatory response with an exaggerated production of several chemokines and proinflammatory cytokines, suggesting the pivotal role of these phagocytic cells in this fungal infection during the early course of infection (Pino-Tamayo et al, 2016).…”

“…In the case of systemic and endemic mycoses, there are scant studies that link the IL-17 and/or neutrophils with the development of a chronic inflammatory process or with fibrosis development. Some studies have demonstrated the presence of neutrophils in pulmonary infiltrating cells during infections by P. brasiliensis (Gonzalez and Cano, 2001;Gonzalez et al, 2003), H. capsulatum (Baughman et al, 1986), C. posadasii (Hung et al, 2005), and B. dermatitidis (Lorenzini et al, 2017). However, as mentioned above, the role of neutrophils during these dimorphic fungal infections is not clear; moreover, their participation in the immune response appears to depend on the phase of infection (acute or chronic) (Pino-Tamayo et al, 2016;Puerta-Arias et al, 2016).…”