Some characteristics of hyperreactivity to bacterial lipopolysaccharide induced in mice by Trypanosoma cruzi infection

Abstract

Mice infected with T. cruzi, Y strain, acquire a high level of susceptibility to the effects of bacterial gram-negative LPS. The LD50 of adult female SW mice to LPS from S. typhosa, decreases from 450 to 2,5 mcg 10-12 days after T. cruzi infection. This hyperreactivity to LPS induced by T. cruzi presents all the characteristics of that found in infection caused by many other agents. During the acute phase of experimental infection with T. cruzi Y strain, mice generally die with a hypovolemic shock very similar to that induced in uninfected animals injected with an adequate dose of bacterial endotoxin. There is evidence for and against the hypothesis that LPS absorbed from the intestinal tract may be involved in the mechanism of death of mice during the acute phase of T. cruzi infection.

IL-10 up-regulates nitric oxide (NO) synthesis by lipopolysaccharide (LPS)-activated macrophages: improved control ofTrypanosoma cruziinfection

“…In parallel with its stimulating effect on the production of inflammatory mediators, administration of LPS during T. cruzi infection resulted in early mortality [ 41, 42]. In this setting, rIL‐10 administration might not only protect against the acute cytokine‐mediated pathology as indicated by previous studies in experimental endotoxaemia [ 12, 43], but also promote parasite clearance by enhancing NO synthesis, as suggested by the in vitro observations reported in the present study.…”

Unraveling the lethal synergism between Trypanosoma cruzi infection and LPS: A role for increased macrophage reactivity

“…As the reports of increased LPS reactivity 17 and decreased macrophage reactivity 23 during T. cruzi infection were based on findings with different T. cruzi stocks, Y strain blood trypomastigotes and DM‐28c clone axenic culture metacyclics, respectively, we tested whether infections caused by the two stocks lead to different outcomes upon LPS‐induced shock. Infection with 10 4 DM‐28c clone trypomastigotes sensitized BALB/c mice to lethal LPS‐induced shock when either blood trypomastigotes or axenic culture metacyclics (as performed by Freire‐de‐Lima et al 23) were used, requiring a longer interval between infection and LPS administration than Y strain blood trypomastigotes (Fig.…”

“…In fact, T. cruzi ‐infected mice are susceptible to lethal shock upon inoculation of low TNF amounts 13, but they also hyperproduce TNF and die of septic shock under various circumstances, such as in the absence of IL‐10 production 14 or under polyclonal T cell activation 15, 16. T. cruzi ‐infected mice are known to be highly susceptible to LPS‐induced shock 17 and to release high amounts of TNF in response to LPS administration 18, a phenomenon originally thought to result from macrophage stimulation 19. An obvious assumption to explain these latter findings would be that T. cruzi , by promoting the release of IFN‐γ at an early stage 20 or priming a Shwartzman‐like reaction through inflammatory T. cruzi glycolipids 21, activates macrophages to release high amounts of TNF upon LPS stimulation, much like other sensitizations to endotoxemia.…”