Contribution of C5-mediated mechanisms to host defence against Echinococcus granulosus hydatid infection.
The aim of this work was to investigate the contribution of complement C5-mediated mechanisms, with an emphasis on inflammation, to host defences against Echinococcus granulosus hydatid disease. Thus, we compared the systemic and local inflammatory responses induced by the parasite, and the outcome of infection, between congenic C5-sufficient (B10.D2 n/SnJ) and C5-deficient (B10.D2 o/SnJ) mice challenged with protoscoleces. Indirect evidence of in-vivo complement activation during the establishment phase was obtained; infection induced serum amyloid P and eosinophil responses which were dependent on C5. Early recruitment of polymorphonuclear cells was not dependent on the presence of C5. The higher capacity of C5-sufficient mice to recruit eosinophils was also observed during the cystic phase of infection, and mice recruiting more eosinophils developed lower parasite masses. Analysis of the outcome of infection after 8 months showed that C5-sufficient mice were more resistant to infection than C5-deficient mice in terms of individuals with no cysts; this trend was not statistically significant. In addition, C5-deficient mice developed higher numbers of large (> 5 mm in diameter) cysts and higher cyst weights than C5-sufficient mice indicating that C5-mediated mechanisms are detrimental for parasite growth. Taken together, our results suggest that complement, through C5-mediated effectors, contributes to host defences by both restricting the establishment of infection and controlling the growth of established cysts. This contribution may, at least partially, be associated with the ability of C5a to promote eosinophil infiltration.
Ferreira
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AM
Cátedra de Inmunología, Facultad de Ciencias/Facultad de Química, Universidad de la República, Casilla de Correos 1157, Montevideo, Uruguay.
Breijo
M
M
Sim
R B
RB
Nieto
A
A
D000818:Animals; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D003182:Complement C5 / Q000172:deficiency / Q000276:immunology* / Q000378:metabolism; D004443:Echinococcosis / Q000276:immunology* / Q000469:parasitology; D004446:Echinococcus / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D000683:Serum Amyloid P-Component / Q000032:analysis
D003176:Complement C3; D003182:Complement C5; D000683:Serum Amyloid P-Component