Role of cytokines and major histocompatibility complex restriction in mouse resistance to infection with a natural recombinant strain (type I-III) of Toxoplasma gondii.
Herein we characterized various genetic markers and the biological behavior of a natural recombinant strain of Toxoplasma gondii (P-Br). From nine genetic markers analyzed, three (B1, ROP1, and SAG1) and three (cS10-A6, GRA6, and SAG3) markers belong to parasites from the type I and type III lineages, respectively. The SAG2 and L363 loci were shown to be type I-III chimera alleles. The cB2l-4 microsatellite marker showed a unique haplotype. The P-Br strain presented low virulence in the acute phase of infection and was cystogenic during the chronic infection. The interleukin 12/gamma interferon axis and inducible nitric oxide synthase were main determinants of resistance during the acute infection with the P-Br strain. As opposed to infection with the type II strain of T. gondii (ME-49), peroral infection with the P-Br strain led only to a light inflammatory infiltrate and no major lesions in the intestine of the C57BL/6 mice. In addition, the BALB/c (resistant to ME-49) and C57BL/6 (susceptible to ME-49) mice were shown, respectively, to be more susceptible and more resistant to cyst formation and toxoplasmic encephalitis when infected with the P-Br strain. Further, the C57BL/KsJ and DBA2/J congenic strains containing major histocompatibility complex (MHC) haplotype "d" were more resistant than the parental strains (C57BL/6 and DBA1/J), when infected with the ME-49 but not with the P-Br strain. Together, our results indicate that resistance to cyst formation and toxoplasmic encephalitis induced during infection with P-Br is not primarily controlled by the MHC haplotype d, as previously reported for type II strains of T. gondii.
Laboratory of Immunopathology, René Rachou Research Center, Oswaldo Cruz Foundation, University of Minas Gerais, Brazil. blimafux@cpqrr.fiocruz.br
Blima
B
Fux
Cibele V
CV
Rodrigues
Ricardo W
RW
Portela
Neide M
NM
Silva
Chunlei
C
Su
David
D
Sibley
Ricardo W A
RW
Vitor
Ricardo T
RT
Gazzinelli
D000818:Animals; D016207:Cytokines / Q000502:physiology*; D006239:Haplotypes; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D008285:Major Histocompatibility Complex / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D019001:Nitric Oxide Synthase / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D011995:Recombination, Genetic; D014122:Toxoplasma / Q000235:genetics; D014124:Toxoplasmosis, Animal / Q000276:immunology*
D016207:Cytokines; D018664:Interleukin-12; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse