Effects of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor alpha on Trypanosoma cruzi trypomastigotes.
We have previously shown that the addition of exogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) to nonactivated mouse peritoneal macrophages (MPM) limits Trypanosoma cruzi infections in vitro (E. Olivares Fontt and B. Vray, Parasite Immunol. 17:135-141, 1995). Lower levels of infection were correlated with a higher level of production of tumor necrosis factor alpha (TNF-alpha) in the absence of nitric oxide (NO) release. These data suggested that GM-CSF and/or TNF-alpha might have a direct parasitocidal effect on T. cruzi trypomastigotes, independently of NO release. To address this question, T. cruzi trypomastigotes were treated with recombinant murine GM-CSF (rmGM-CSF), recombinant murine TNF-alpha (rmTNF-alpha), or both cytokines in a cell-free system. Treatment with rmGM-CSF but not rmTNF-alpha caused morphological changes in the parasites, and most became spherical after 7 h of incubation. Both cytokines exerted a cytolytic activity on the trypomastigotes, yet the trypanolytic activity of rmTNF-alpha was more effective than that of rmGM-CSF. Viable rmGM-CSF- and rmTNF-alpha-treated parasites were less able to infect MPM than untreated parasites, and this reduction in infectivity was greatest for rmGM-CSF. Treatments with both cytokines resulted in more lysis and almost complete inhibition of infection. The direct parasitocidal activity of rmTNF-alpha was inhibited by carbohydrates and monoclonal antibodies specific for the lectin-like domain of TNF-alpha. Collectively, these results suggest that cytokines such as GM-CSF and TNF-alpha may directly control the level of T. cruzi trypomastigotes at least in vitro and so could determine the outcome of infection in vivo.
Olivares Fontt
E O
EO
Laboratoire d'Immunologie Expérimentale, Faculté de Médecine, Université Libre de Bruxelles, Vrije Universiteit Brussel, Brussels, Belgium.
De Baetselier
P
P
Heirman
C
C
Thielemans
K
K
Lucas
R
R
Vray
B
B
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D011994:Recombinant Proteins / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000166:cytology / Q000187:drug effects* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*; D014774:Virulence / Q000187:drug effects
D011994:Recombinant Proteins; D014344:Trypanocidal Agents; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor