Rhodococcus equi experimental infection: macrophage activation in drug-immunosuppressed mice

Rhodococcus equi experimental infection: macrophage activation in drug-immunosuppressed mice.

THESIS: R. Diniz submitted this dissertation for her Masters in Tropical Diseases at Botucatu School of Medicine, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil, 1999.

Advisor: Professor Silvio Luis de Oliveira

^{Address to correspondence}

ABSTRACT:Rhodococcus equi, a widely distributed Gram-positive bacteria, is a pneumonia agent in foals and AIDS patients. As a facultative intracellular parasite, it causes granulomatous lesions of difficult access for chemotherapics and antibiotics. Some assays have shown the importance of T cells, cytokines, and activated macrophages in host resistance against R. equi. In this study, an experimental model of R. equi infection was performed by treating BALB/c inbred mice with immunosuppressive drugs, which induce modifications in the host resistance pattern. Mice were inoculated with ATCC 33701+ R. equi and treated with dexamethasone, indomethacin, or cyclophosphamide at the beginning of infection. Bacteria were recovered from spleen, liver, and lung fragments. Hydrogen peroxide (H₂O₂) and nitric oxide (NO) production by peritoneal macrophage cultures were determined by phenol red oxidation and Griess reaction, respectively. The highest bacterial recovery was observed in drug-immunosuppressed animals, mainly in cyclophosphamide treated-animals. Bacterial recovery was higher in the liver, followed by spleen and lung. NO production decreased at the beginning of infection in infected and treated animals. H₂O₂ production was low in all periods and groups. There was an inverse association between NO production and bacterial recovery at the beginning of infection. There was a decrease in bacterial recovery after a NO production increase in drug-treated animals after seven and nine days of infection. NO decrease may lead to bacteria dissemination and justify the high susceptibility of immunosuppressed hosts. H₂O₂ seems to have no important role in R. equi infection control. New studies should be performed to understand the real role of NO in R. equi infection control and its function in human and horse macrophages.

KEY WORDS:Rhodococcus equi; experimental infection; macrophages, immunosuppressive drugs; BALB/c mice.

Publication Dates

• Publication in this collection
  09 Dec 2003
• Date of issue
  2003