title: IFN-gamma, but not nitric oxide or specific IgG, is essential for the in vivo control of low-virulence Sylvio X10/4 Trypanosoma cruzi parasites.
abstract: Highly virulent strains of Trypanosoma cruzi are frequently used as murine models of Chagas' disease. However, these strains do not fully represent the spectrum of parasites involved in the human infection. In this paper, we analysed parasitaemia, mortality, tissue pathology and parasite-specific IgG serum levels in immune-deficient mice infected with Sylvio X10/4 parasites, a T. cruzi derived from a chagasic patient that yields very low parasitaemias and in C3H/HePAS mice induces a chronic cardiopathy resembling the human disease. IFN-gamma was identified as a crucial element for parasite control as its absence determined a drastic increase in parasitaemia, tissue parasitism, leukocyte infiltrates at the heart and striated muscles and mortality. The lack of IFN-gamma or IL-12p40, a molecule shared by IL-12 and IL-23, also resulted in spinal cord lesions and a progressive paralysis syndrome. Whereas IgG2a was the main Ig isotype in infected C57BL/6 mice, IL-12p40-KO mice produced IgG2a and IgG1 and IFN-gamma-KO mice produced only IgG1. The IFN-gamma-protective effect was not essentially mediated by nitric oxide (NO), inasmuch as infected iNOS-KO mice showed no parasitaemia and low tissue damage. Mice deficient in CD4(+) or CD8(+) T cells showed an intermediate phenotype with increased mortality and tissue pathology but no parasitaemia. Interestingly, CD28-KO mice were unable to produce anti-T. cruzi IgG antibodies but presented moderate tissue pathology and managed to control the infection. Thus, differently from infections with high virulence parasites, neither IgG, NO nor CD28-mediated signalling are essential for the non-sterile control of Sylvio X10/4 parasites.
authors.affiliation: Department of Immunology, Biomedical Sciences Institute, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: C R F
authors.initials: CR
authors.lastname: Marinho
authors.forename: L N
authors.initials: LN
authors.lastname: Nuñez-Apaza
authors.forename: R
authors.initials: R
authors.lastname: Martins-Santos
authors.forename: K R B
authors.initials: KR
authors.lastname: Bastos
authors.forename: A L
authors.initials: AL
authors.lastname: Bombeiro
authors.forename: D Z
authors.initials: DZ
authors.lastname: Bucci
authors.forename: L R
authors.initials: LR
authors.lastname: Sardinha
authors.forename: M R D
authors.initials: MR
authors.lastname: Lima
authors.forename: J M
authors.initials: JM
authors.lastname: Alvarez
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D002460:Cell Line; D002598:Chagas Cardiomyopathy / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D009569:Nitric Oxide / Q000502:physiology; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D009569:Nitric Oxide; D007371:Interferon-gamma