Paracoccidioidomycosis: a sequential histopathologic study of lesions in experimentally-infected rats

Abstract

SUMMARYFemale albino rats were used for the sequential histopathological study of experimental paracoccidioidomycosis. The animals were inoculated intraperitoneally with a strain of Paracoccidioides brasiliensis in the yeast-like phase, and sacrificed at given intervals from 1 to 168 days after inoculation; each animal received an inoculum of 4 x 10^ cells in 0.8 ml of saline. The control group received saline containing scrapings of the culture medium.Tissue from the inoculation site was examined. The cellular population, the extracellular matrix, and the presence and characteristics of fungi were analysed in the inflammatory granulomatous process by light microscopy.The results allowed to separate the kinetic of the inflammatory response into three stages: 1) neutrophilic or macrophagic-neutrophilic; 2) pre-granulomatous; 3) granulomatous.Synthesis of the extracellular matrix began with the depositing of fibrin-like material, and increased gradually with deposits of collagen, proteoglycans, and glycoproteins. Parasites were present in all of the examined periods.Recurrences of the disease were clearly shown through the concurrence of recently-formed granulomas with older granulomas, implying that this type of granulomatous process does not eliminate the disease, nor is it able to limit fungal dissemination over a prolonged period of time.

Role of Dectin‐1 receptor on cytokine production by human monocytes challenged with Paracoccidioides brasiliensis

“…IL-8 release is important to attract neutrophils (PMN) to the infection site, once it has been shown a massive infiltration of these cells in infected tissues of PCM patients and in the early phase of experimentally infected animals . [59][60][61][62] In addition, PMN effector and modulator new mechanisms have been shown to participate in the response to this fungus, demonstrating the importance of this cytokine in PMN recruitment, activation and survival. 31,32,35,63,64 Thus, it has been shown a cross-talk between PI3-Kinase and NF-Kappa B pathways in TNF-alpha-stimulated PMN, resulting in NF-Kappa B ⁄ ERK1 ⁄ 2-dependent IL-8 production that acts in an autocrine manner, evidencing other pathways in the induction of IL-8.…”

Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia

“…In our PCM murine model, the sequential histophatological studies have revealed the kinetics of the inflammatory response consisting of three stages: (i) a neutrophilic or monocyte-neutrophilic stage, in which PMN and histiocytes are present, witnessing the early inflammatory process; (ii) a mixed granulomatous stage, in which epithelioid granulomata run in parallel with the presence of PMN and (iii) a granulomatous and fibrous-fibroblastic stage, characterized by presence of abundant giant cells, histiocytes, macrophages and fibrous conjunctive tissue [27,28,31,32].…”

Participation of dectin-1 receptor on NETs release against Paracoccidioides brasiliensis: Role on extracellular killing

“…Due to massive infiltration of neutrophils (PMNs) found in the inflammatory sites of human disease (Franco and Montenegro, 1982) and in different experimental models (Iabuki and Montenegro, 1979;Kerr et al, 1988;Calich, 1994), probably as a result of chemokines action (Souto et al, 2003), these cells have attracted the attention of the researchers in recent times. It is suggested that chemokines can be released by macrophages that have established an initial contact with the fungus (Calich et al, 1985).…”