title: Immune system pathogenesis is prevented by the neutralization of the systemic trans-sialidase from Trypanosoma cruzi during severe infections.
abstract: During the acute phase of Trypanosoma cruzi infection, strong haematological and immune system alterations are observed. The parasite expresses trans-sialidase, a virulence factor responsible for the sialylation of its surface glycoconjugates. This enzyme is also shed to the bloodstream where it is associated with immune system alterations triggered during the infection. During experimental and human infections, the host elicits antibodies able to neutralize the enzyme activity that would be responsible for restricting systemic trans-sialidase to the early steps of the infection, when major immune alterations are induced. The actual relevance of these antibodies was tested by passive transference of monoclonal neutralizing antibodies in acute infection models displaying extreme sensitivity to the infection. Mice were inoculated with virulent parasite strains that induce high parasitaemia, early mortality and strong immune tissue abnormalities. The trans-sialidase-neutralizing antibodies were able to preserve B cell areas both in ganglia and spleen as well as the thymus architecture even in these extreme models. Although no differences between control and treated mice regarding animal survival were found, a major role for the humoral response in controlling the damage of the immune system induced by a systemically distributed virulence factor was defined in an infection with a eukaryotic pathogen.
authors.affiliation: Departamento de Microbiología, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: M G
authors.initials: MG
authors.lastname: Risso
authors.forename: T A
authors.initials: TA
authors.lastname: Pitcovsky
authors.forename: R L
authors.initials: RL
authors.lastname: Caccuri
authors.forename: O
authors.initials: O
authors.lastname: Campetella
authors.forename: M S
authors.initials: MS
authors.lastname: Leguizamón
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D005724:Ganglia / Q000473:pathology; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D007116:Immunization, Passive; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D009500:Neutralization Tests; D018512:Parasitemia; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D006023:Glycoproteins; C069715:trans-sialidase; D009439:Neuraminidase