Elicitation of specific, Th1-biased immune response precludes skeletal muscle damage in cruzipain-vaccinated mice.
Cruzipain (Cz), the major cystein proteinase of Trypanosoma cruzi, is able to induce protective immunity against parasite challenge. However, some concern has arisen regarding its potential to elicit pathogenic autoimmune reactivity. To determine whether the adverse myopathic effects of Cz-based immunization could be prevented, we evaluated the co-administration of Cz with different adjuvants. Mice were immunized with Cz adjuvantized by alum (Cz+alum), oligodeoxynucleotides containing CpG motifs (Cz+ODN-CpG) or Freund's preparation (Cz+CFA). Cz triggered a vigorous specific humoral response, irrespective of the adjuvant used. Alum mainly drove response towards Th2 phenotype, characterized by specific IgG1 antibodies and IL-10 induction, whereas Cz+ODN-CpG mice exhibited Th1-dominant immunity, with antibodies of the IgG2a isotype and enhanced IFN-gamma production. Histological examination of cardiac tissue demonstrated lesions in Cz+CFA but not in Cz+alum nor Cz+ODN-CpG immunized animals, suggesting that CFA is critical for Cz-mediated injury. Analysis of skeletal muscle revealed that mice receiving Cz+CFA exhibited disrupted and hyalinized myofibers, whereas [Cz+alum]-immunized animals showed hyalinization, architecture modifications and small inflammatory foci. Conversely, no abnormalities were observed in the striated muscle from the Cz+ODN-CpG group. Hence, generation of specific immune response skewed towards Th1, as that recorded for the ODN-CpG adjuvant, may preclude triggering of Cz-mediated muscle tissue damage.
Frank
F M
FM
Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral (IDEHU), CONICET-UBA, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina. ferfrank@ffyb.uba.ar
Cazorla
S I
SI
Sartori
M J
MJ
Corral
R S
RS
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D006801:Humans; D007107:Immune System / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D018482:Muscle, Skeletal / Q000276:immunology / Q000473:pathology*; D015800:Protozoan Proteins; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000378:metabolism
D000276:Adjuvants, Immunologic; D015800:Protozoan Proteins; D003546:Cysteine Endopeptidases; C063214:cruzipain