In vitro study of acute Trypanosoma cruzi infection in 2 murine strains of different susceptibility. Immunomodulation with LPS, pentoxyphilline, and gamma-interferon

PEREZ A, TAMAE-KAKAZU M, ROGGERO E, SERRA E, REVELLI S, WIETZERBIN J, BOTTASSO O

Revista Medica de Rosario

CMR

Año: 2003 vol. 69 p. 23 - 35

0327-5019

Infection with T. cruzi in BALB/c and C57BL/6 mice leads to an acute disease characterised by marked parasitemia, spleen and lymph node enlargement, inflammatory infiltrates and thymic atrophy. The disease is 100% lethal in C57BL/6 mice, whereas 60% of BALB/c mice recovered. Given this background, we have now studied whether such disease-outcome differences bear some relationship with the in vitro behaviour of peritoneal macrophages (Mf) to their encounter with T. cruzi. There were no between-strain differences as to the number of intracellular parasites and NO derivatives in culture supernatants, this not being the case for TNFa whose levels were significantly higher in cultures from C57BL/6 mice. To ameliorate the latter response, C57BL/6 mice were next subjected to an in vivo  desensitization with LPS and PTx, and their Mf were further exposed in vitro  to T. cruzi. This resulted in a decreased production of inflammatory cytokines, but an increased number of amastigote counts, that were lowered when adding IFNg to in vitro cultures. Increased severity of acute T. cruzi in C57BL/6 mice does not seem to be related with a greater parasite load, but to an excessive synthesis of inflammatory cytokines.