[show abstract][hide abstract] ABSTRACT: 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.
Infection and immunity 01/2011; 79(4):1741-9. · 4.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Chemokines are a superfamily of low-molecular-weight cytokines that were initially described for their chemoattractant activity. It is now clear chemokines have several other activities that modulate immune processes. Chemokines appear to play a role in the pathogenesis of several inflammatory diseases. The role of chemokines and their receptors in mediating granulomatous inflammation induced by Schistosoma mansoni egg antigens presented in particulate manner have been studied in detail. Much less is known of the role of chemokines in mediating inflammation during the course of S. mansoni infection. Our studies in mice suggest a relevant role for the chemokine CCL3 and the receptor CCR5 in the pathogenesis of experimental S. mansoni infection. Absence of CCL3 is associated with decrease in granuloma size, fibrosis and parasite load. In humans, levels of CCL3 in plasma associate with disease severity and may be useful for diagnostic purposes. In contrast, absence of CCR5 is associated with enhanced lethality, granuloma size and fibrosis. It is suggested that the balance of chemokine production and chemokine receptor activation are important determinants of the fate of infection in experimental animals and humans.
[show abstract][hide abstract] ABSTRACT: Resistant (Taim, RS) and susceptible albino (Joinville, SC) Biomphalaria tenagophila populations were kept together, at different proportions, throughout a 18-month-period. Some of the snail groups were submitted to Schistosoma mansoni infection. The targets of this study were (a) to analyze the populational dynamics among resistant and susceptible individuals to S. mansoni; (b) to study the resistance phenotype in descendants of cross-breeding; (c) to observe whether the parasite could exert any kind of selection in those snail populations. Throughout the experiment it could be observed that the susceptible B. tenagophila strain (Joinville) underwent a selective pressure of the parasite that was negative, since the individuals showed a high mortality rate. Although B. tenagophila (Taim) population presented a higher mortality rate without pressure of the parasite, this event was compensated by a reproductive capacity. B. tenagophila Taim was more fecund than B. tenagophila Joinville and was able to transmit the resistance character to their descendants. F1 generation obtained by cross-breeding between resistant and susceptible lineages was completely resistant to S. mansoni infection, irrespective of the Taim proportion. Moreover, less than 5% of F2 progeny were susceptible to S. mansoni infection.
Memórias do Instituto Oswaldo Cruz 10/2006; 101 Suppl 1:247-51. · 1.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: In human schistosomiasis, the concentrations of the chemokine macrophage inflammatory protein 1alpha (MIP-1alpha/CCL3) is greater in the plasma of patients with clinical hepatosplenic disease. The objective of the present study was to confirm the ability of CCL3 to detect severe disease in patients classified by ultrasonography (US) and to evaluate the potential role of CCL3 in Schistosoma mansoni-infected mice. CCL3 was measured by enzyme-linked immunosorbent assay in the plasma of S. mansoni-infected patients. CCL3-deficient mice were infected with 25 cercariae, and various inflammatory and infectious indices were evaluated. The concentration of CCL3 was higher in the plasma of S. mansoni-infected than noninfected patients. Moreover, CCL3 was greater in those with US-defined hepatosplenic than with the intestinal form of the disease. In CCL3-deficient mice, the size of the granuloma and the liver eosinophil peroxidase activity and collagen content were diminished compared to wild-type mice. In CCL3-deficient mice, the worm burden after 14 weeks of infection, but not after 9 weeks, was consistently smaller. The in vitro response of mesenteric lymph node cells to antigen stimulation was characterized by lower levels of interleukin-4 (IL-4) and IL-10. CCL3 is a marker of disease severity in infected humans, and experimental studies in mice suggest that CCL3 may be a causative factor in the development of severe schistosomiasis.
Infection and Immunity 05/2005; 73(4):2515-23. · 4.07 Impact Factor