Phagocytic cells play an important role in nonspecific resistance to
fungal infection by mediating an inflammatory response and by a direct fungicidal action. In this study, the functional activity of peritoneal macrophages obtained from hamsters experimentally infected with strain Pb18 of Paracoccidioides brasiliensis was evaluated during 16 weeks of
infection. The results showed that macrophages had a higher spreading ability associated with increased production of
tumor necrosis factor alpha (
TNF-alpha) and enhanced fungicidal activity during the early periods of
infection.
TNF-alpha levels remained elevated during all periods studied, while low levels of
interleukin-1 beta (IL-1 beta) were produced during the
infection. A necrotic area with dead fungi was observed at the inoculation site and the
infection disseminated only to liver and lymph nodes in a few animals. These results suggest that during the early stages of
infection with P. brasiliensis, macrophage activation by the high levels of
TNF-alpha limited fungal dissemination. In contrast, in the later stages of
infection, high levels of
TNF-alpha were observed while the fungicidal activity of macrophages was lower and the animals presented loss of vitality resulting in their death. These observations suggest a complex role of
TNF-alpha in experimental
paracoccidioidomycosis of Syrian hamsters, involving not only resistance but also pathogenesis.