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.