IL-10 mediates susceptibility to Trypanosoma cruzi infection.
IL-10 has been shown to inhibit some aspects of macrophage activation, including the in vitro IFN-gamma-mediated intracellular killing of the protozoan parasite Trypanosoma cruzi. We have previously shown that genetically susceptible mice produced more IL-10 during T. cruzi infection than resistant mice, suggesting an association between IL-10 production and disease susceptibility. In the present study, such an association was documented. IL-10 mRNA was present in the spleens of susceptible C57BL/6 mice, but not in resistant (C57BL/6 x DBA/2) F1 mice, as early as 2 days after infection with T. cruzi. In susceptible mice, IL-10 mRNA was found in enriched populations of splenic T cells and peritoneal macrophages by 4 days after infection. By 14 days after infection, IL-10 mRNA was detected in enriched populations of splenic T cells and peritoneal macrophages, as well as by splenic B cells and macrophages. In SCID mice infected with T. cruzi, IL-10 mRNA was detected in peritoneal cells 2 days after infection. The IL-10 mRNA production was not abolished by treatment with anti-asialo GM-1 Ab before infection, which is consistent with its production by macrophages. Finally, the role of endogenous IL-10 production in the susceptibility to T. cruzi infection was demonstrated by the protection of highly susceptible C57BL/6 mice against acute disease and death from T. cruzi by the administration of neutralizing anti-IL-10 mAb. This study demonstrated an important and perhaps essential role of IL-10 in mediating in vivo susceptibility to T. cruzi infection.
Reed
S G
SG
Infectious Disease Research Institute, Seattle, WA 98109.
Brownell
C E
CE
Russo
D M
DM
Silva
J S
JS
Grabstein
K H
KH
Morrissey
P J
PJ
D000818:Animals; D001483:Base Sequence; D014355:Chagas Disease / Q000276:immunology*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D013154:Spleen / Q000166:cytology; D014349:Trypanosoma cruzi / Q000276:immunology*
D017931:DNA Primers; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma