Resistance to Trypanosoma cruzi infection in mice does not necessarily correlate with production of interferon-gamma in vivo.
Interferon-gamma (IFN-gamma) is the most important mediator of inhibition of intracellular replication of Trypanosoma cruzi in vitro and has a protective effect against this parasite if administered in vivo. Here we have analyzed the importance of IFN-gamma for resistance against a lethal infection with T. cruzi in a mouse model system. Resistant B6D2 mice survived the infection with a virulent strain of T. cruzi, whereas susceptible BALB/c mice died within 3 weeks. Both strains produced large amounts of IFN-gamma after infection. Surprisingly, susceptible mice had higher serum concentrations of IFN-gamma and showed, using in situ hybridization a stronger increase in IFN-gamma mRNA-producing cells in their spleens than resistant mice. Moreover, this pattern was also found when immune spleen cells were stimulated with parasite antigens in vitro. However, a marked difference between these mice was found in the production of IL-4, which was much higher in susceptible mice in vivo and in vitro. No difference was found for IL-10. These data show that, at least in the mouse strain/parasite combination used, production of IFN-gamma is not the decisive factor determining resistance or susceptibility to T. cruzi. Rather, it is possible that the balance between protective (e.g., IFN-gamma) and exacerbative cytokines (e.g., IL-4) may decide over disease control or progression.
Meyer zum Büschenfelde
C
C
Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Cramer
S
S
Fleischer
B
B
Frosch
S
S
D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D014355:Chagas Disease / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D013462:Sulfur Radioisotopes / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology*
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma