Experimental infection with Schistosoma mansoni in CCR5-deficient mice is associated with increased disease severity, as CCR5 plays a role in controlling granulomatous inflammation.
The plasma level of the chemokine CCL3 is elevated in patients with chronic severe schistosomiasis mansoni. We have previously shown that CCL3(-/-) mice with experimental infection showed diminished pathology and worm burden compared to those of wild-type (WT) mice. To elucidate further the role of CC chemokines during schistosomiasis mansoni infection, we evaluated the course of infection in C57BL/6J mice deficient in CCR5, one of the receptors for CCL3. The CCR5 deficiency proved to be remarkably deleterious to the host, since mortality rates reached 70% at 14 weeks postinfection in CCR5(-/-) mice and 19% in WT mice. The increased lethality was not associated with an increased parasite burden, since similar numbers of eggs and adult worms were found in mice from both groups. Liver granulomas of chronically infected CCR5(-/-) mice were larger and showed greater numbers of cells and collagen deposition than liver granulomas from WT mice. This was associated with higher levels of production of intereleukin-5 (IL-5), IL-13, CCL3, and CCL5 in infected CCR5(-/-) mice than in infected WT mice. Moreover, at 8 weeks after infection, just before changes in pathology and mortality, the numbers of FoxP3-positive cells were lower in liver granulomas of CCR5(-/-) mice than in WT mice. In conclusion, the CCR5 deletion is deleterious to mice infected with Schistosoma mansoni, and this is associated with enhanced fibrosis and granulomatous inflammation.
Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Adriano L S
AL
Souza
Patrícia R S
PR
Souza
Cíntia A
CA
Pereira
Adriana
A
Fernandes
Rodrigo
R
Guabiraba
Remo C
RC
Russo
Leda Q
LQ
Vieira
Ary
A
Corrêa
Mauro M
MM
Teixeira
Deborah
D
Negrão-Corrêa
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006099:Granuloma / Q000276:immunology / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019713:Receptors, CCR5 / Q000172:deficiency* / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology; D012552:Schistosomiasis / Q000276:immunology / Q000473:pathology
D019713:Receptors, CCR5
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