In vivo infection by Trypanosoma cruzi: the conserved FLY domain of the gp85/trans-sialidase family potentiates host infection.
Trypanosoma cruzi is a protozoan parasite that infects vertebrates, causing in humans a pathological condition known as Chagas' disease. The infection of host cells by T. cruzi involves a vast collection of molecules, including a family of 85 kDa GPI-anchored glycoproteins belonging to the gp85/trans-sialidase superfamily, which contains a conserved cell-binding sequence (VTVXNVFLYNR) known as FLY, for short. Herein, it is shown that BALB/c mice administered with a single dose (1 μg/animal, intraperitoneally) of FLY-synthetic peptide are more susceptible to infection by T. cruzi, with increased systemic parasitaemia (2-fold) and mortality. Higher tissue parasitism was observed in bladder (7·6-fold), heart (3-fold) and small intestine (3·6-fold). Moreover, an intense inflammatory response and increment of CD4+ T cells (1·7-fold) were detected in the heart of FLY-primed and infected animals, with a 5-fold relative increase of CD4+CD25+FoxP3+ T (Treg) cells. Mice treated with anti-CD25 antibodies prior to infection, showed a decrease in parasitaemia in the FLY model employed. In conclusion, the results suggest that FLY facilitates in vivo infection by T. cruzi and concurs with other factors to improve parasite survival to such an extent that might influence the progression of pathology in Chagas' disease.
Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, Brasil.
R R
RR
Tonelli
A C
AC
Torrecilhas
J F
JF
Jacysyn
M A
MA
Juliano
W
W
Colli
M J M
MJ
Alves
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology* / Q000469:parasitology; D017124:Conserved Sequence; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006023:Glycoproteins / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000737:chemistry* / Q000276:immunology; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry; D010537:Peritoneum / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014349:Trypanosoma cruzi / Q000201:enzymology / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D006023:Glycoproteins; D053645:Interleukin-2 Receptor alpha Subunit; D010455:Peptides; C069715:trans-sialidase; D009439:Neuraminidase