Type I IFNs stimulate nitric oxide production and resistance to Trypanosoma cruzi infection.
The participation of type I IFNs (IFN-I) in NO production and resistance to Trypanosoma cruzi infection was investigated. Adherent cells obtained from the peritoneal cavity of mice infected by the i.p. route produced NO and IFN-I. Synthesis of NO by these cells was partially inhibited by treatment with anti-IFN-alphabeta or anti-TNF-alpha Abs. Compared with susceptible BALB/c mice, peritoneal cells from parasite-infected resistant C57BL/6 mice produced more NO (2-fold), IFN-I (10-fold), and TNF-alpha (3.5-fold). Later in the infection, IFN-I levels measured in spleen cell (SC) cultures from 8-day infected mice were greater in C57BL/6 than in infected BALB/c mice, and treatment of the cultures with anti-IFN-alphabeta Ab reduced NO production. IFN-gamma or IL-10 production by SCs was not different between the two mouse strains; IL-4 was not detectable. Treatment of C57BL/6 mice with IFN-I reduced parasitemia levels in the acute phase of infection. Mice deprived of the IFN-alphabetaR gene developed 3-fold higher parasitemia levels in the acute phase in comparison with control 129Sv mice. Production of NO by peritoneal macrophages and SCs was reduced in mice that lacked signaling by IFN-alphabeta, whereas parasitism of macrophages was heavier than in control wild-type mice. We conclude that IFN-I costimulate NO synthesis early in T. cruzi infection, which contributes to a better control of the parasitemia in resistant mice.
Costa
Vlaudia M A
VM
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
Torres
Karen C L
KC
Mendonça
Ronaldo Z
RZ
Gresser
Ion
I
Gollob
Kenneth J
KJ
Abrahamsohn
Ises A
IA
D000818:Animals; D002478:Cells, Cultured; D014355:Chagas Disease / Q000378:metabolism* / Q000469:parasitology / Q000517:prevention & control*; D005260:Female; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis*; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000378:metabolism / Q000469:parasitology; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016898:Interferon-alpha; D017471:Receptors, Interferon; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D016899:Interferon-beta; D007371:Interferon-gamma