Natural killer cell activity in experimental paracoccidioidomycosis of the Syrian hamster

Abstract

The study evaluated the activity of NK cells during the course of experimental infection of hamsters with Paracoccidioides brasiliensis. Eigthy hamsters were infected with P. brasiliensis by intratesticular route and sacrificed at 24h, 48h, 96h, 1, 2, 4, 8 and 11 weeks of infection and compared to 40 noninfected hamsters employed as controls. These animals were submitted to the study of NK cytotoxic activity by a single-cell assay and humoral immune response by immunodiffusion and ELISA tests. The production of macrophage migration inhibitory factor in the presence of Phyto-hemagglutinin and P. brasiliensis antigen and histopathology of the lesions were evaluated at 1, 4, 8 and 11 weeks of infection. The infected animals displayed significantly high levels of NK activity during the four weeks of infection that decreased from the 8th week on when compared to controls. This impairment of NK activity was associated with depression of cell-mediated immune response and with increase in the extension of the histopathologic lesions. There was an inverse correlation between NK cell activity and specific antibody levels. The results suggest that after initial activation, NK cells were unable to control the fungus dissemination. The impairment of NK activity in the late stages of the infection might be related to immunoregulatory disturbances associated with paracoccidioidomycosis.

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

“…At this moment, however, the role of CD4 T cells has not been elucidated. In another study, NK cells were unable to control fungal infection [54].…”

Role of TLR2 and TLR4 in Human Neutrophil Functions AgainstParacoccidioides brasiliensis

“…The infection can be acquired by inhalation of airborne conidia that reach the lung alveoli, where they transform into yeast cells, the infective form [1]. Many people are exposed to the fungus, but only a small number develop clinical symptoms, suggesting that both innate and adaptive mechanisms are important in fungus clearance [2][3][4][5]. The host innate immune response against fungus has been well characterized, and several studies have clearly shown the role of phagocytic cells.…”

Characterization of cytotoxic immune response in skin and mucosal lesions of paracoccidioidomycosis

“…However, in later stages of the disease, this activity is decreased owing to a depressed cellular immune response, and increase of lesions. In this phase of experimental PCM, NK cells are unable to control the dissemination of the fungi 6,11 . The participation and interaction of NK cells with other cells remain to be determined in human PCM lesions.…”

“…NK cells, in experimental infection by Pb , seem to be related to a depressed immune response with increased lesions late in the infection 6 . Some studies suggest an important role of CD8+ T cells in the control of fungal load 7,8 …”