Effects of fumonisins on selected murine immune responses and infection with Trypanosoma cruzi (Fusarium moniliforme)

Fusarium monliforme, a ubiquitous fungus infecting corn, produces fumonisin mycotoxins, known etiologic agents of many animal diseases. In a study of the immune system effects of fumonisins, in BALB/c mice, the myotropic Brazil strain of Trypanosoma cruzi was used as a host-resistance model. Mice fed diets containing fumonisins provided by Fusarium moniliforme culture material (CM) were infected with T. cruzi. Results indicate that mice fed CM were more resistant to T. cruzi infection as evidenced by decreased blood and tissue parasites. Increased nitric oxide (NO) production by peritoneal macrophages from mice fed fumonisins occurred earlier during T. cruzi infection compared to control mice, possibly accounting for the apparent enhanced resistance to infection. Since sphinganine/sphingosine (sa/so) was increased in organs of mice fed CM, disruption of sphingolipid synthesis was suggested as a possible mechanism of altered NO production patterns. The ability of fumonisins to alter macrophage functions following stimulation with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) was examined in the RAW macrophage cell line. Incubation with 10–50 μM FB1 for 48 hours resulted in a dose-dependent increase in LPS-stimulated NO production. Increased NO production by PMA-stimulated RAW cells occurred with 50 μM FB₁, but was decreased with 1–10 μM. These data suggest a complex interaction between fumonisins and macrophages, resulting in altered macrophage functions.; Three morphological forms of T. cruzi (epimastigotes, trypomastigotes, and amastigotes) were exposed to FB₁ in vitro to investigate a possible interaction between fumonisins and T. cruzi . Concentrations of FB₁ (10–50 μM) that were cytotoxic to murine fibroblasts were not toxic to T. cruzi trypomastigotes and did not affect the ability of T. cruzi to infect and replicate as amastigotes in mammalian cells; however, exposure to 5 or 10 μM FB₁ decreased proliferation of T. cruzi epimastigotes. Therefore, direct toxicity of fumonisins to T .cruzi in vivo is unlikely, especially since FB₁ is poorly absorbed by the gastrointestinal tract. Results suggest that fumonisins affected the murine immune response to T. cruzi, providing a useful host-resistance model for further studying immunotoxic effects of fumonisins.