Search

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.

ABSTRACTThe 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.

We describe the parasitological kinetics and histopathological and immunological alterations in platelet-activating factor receptor-deficient (PAFR(-/-)) and wild-type mice after a single Strongyloides venezuelensis infection (subcutaneous inoculation of 500 L3 larvae). There was no difference in the numbers of worms that reached and became established in the small intestines of PAFR(-/-) and wild-type mice. However, at 12 days after infection, significantly more worms were recovered from PAFR(-/-) mice. Although PAFR(-/-) infected mice showed a delay in elimination of adult worms, worms established in the small intestine of these mice produced a significantly lower number of eggs due to a reduction in worm fecundity. There were also significant reductions in the number of circulating and tissue eosinophils and tumor necrosis factor levels in the small intestines of PAFR(-/-) mice infected for 7 days compared to the number and level in wild-type mice. Histological analysis confirmed the reduced inflammatory process and revealed that the PAFR(-/-) mice had a smaller number of goblet cells. The concentrations of the type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-10 were lower in small intestine homogenates and in supernatants of antigen-stimulated lymphocytes from spleens or mesenteric lymph nodes of PAFR(-/-) mice than in the corresponding preparations from wild-type mice. Thus, in S. venezuelensis-infected PAFR(-/-) mice, decreased intestinal inflammation is associated with enhanced worm survival but decreased fecundity. We suggest that although a Th2-predominant inflammatory response decreases worm survival, the worm may use factors produced during this response to facilitate egg output and reproduction. PAFR-mediated responses appear to modulate these host-derived signals that are important for worm fecundity.