Juvenile Rhesus Monkeys Have Lower Type 2 Cytokine Responses than Adults after Primary Infection withSchistosoma mansoni

Abstract

Adults and children have differences in their susceptibility to schistosomiasis. The relative influences of agedependent innate resistance and acquired immunity in the differences between susceptibility to schistosomiasis are difficult to assess in humans. Therefore, we exposed juvenile and adult female rhesus monkeys to primary infection with Schistosoma mansoni. In contrast to the adult animals, the juvenile rhesus monkeys had low levels of interleukin (IL)-4 and IL-5 production by peripheral blood mononuclear cells after schistosome infection, as well as lower levels of parasite-antigen-specific antibody (IgG, IgM, and IgA) responses, and produced limited antigen-specific or total IgE. Juvenile animals had statistically nonsignificant increased worm burdens and tissue or fecal egg counts, compared with that of adults, whereas circulating schistosome antigens were significantly higher in infected juvenile monkeys. These results suggest that juvenile rhesus monkeys have reduced type 2 cytokine responses after primary schistosome infections and perhaps are more susceptible to parasite infection.Schistosomiasis affects 1250 million people worldwide. The disease is caused by infection with trematode parasites of the Schistosoma species. Extensive epidemiology studies on human populations in endemic countries have shown that adults generally have lower intensities of schistosome infection than do children. The reduced levels of Schistosoma mansoni infections in adults are par-

Impaired Basophil Induction Leads to an Age-Dependent Innate Defect in Type 2 Immunity during Helminth Infection in Mice

“…Juvenile mice are more susceptible than adult mice to primary N. brasiliensis infection Previous studies in juvenile and adult rhesus monkeys demonstrated an increased susceptibility to primary S. mansoni infection in younger animals (21,22). To explore the immunological basis of this, we initially sought to use murine S. mansoni infections, a widely used animal model of many aspects of human schistosome infection (31).…”

“…Previously, rhesus monkeys were used to show that juveniles are more susceptible to primary infection with S. mansoni relative to comparably infected adult monkeys, which is associated with a marked defect in the generation of a range of helminth-specific type 2 responses in younger monkeys (21). The defective ability of juvenile animal hosts to initiate such an im- mune response to helminths is not restricted to rhesus monkeys; it is also seen in rats, with a delayed worm expulsion in juvenile rats following primary infection with N. brasiliensis or S. mansoni (data not shown).…”

“…This age-dependent phenomenon was addressed experimentally using S. mansoni infection of rhesus macaque monkeys (21). Following a primary S. mansoni infection, juvenile monkeys had greater numbers of worms present then did comparable infected adult animals (21,22).…”

“…This age-dependent phenomenon was addressed experimentally using S. mansoni infection of rhesus macaque monkeys (21). Following a primary S. mansoni infection, juvenile monkeys had greater numbers of worms present then did comparable infected adult animals (21,22). Additionally, despite having more worms present, the juvenile monkeys had a strikingly lower type 2 immune response compared with the adult animals (21).…”

“…Following a primary S. mansoni infection, juvenile monkeys had greater numbers of worms present then did comparable infected adult animals (21,22). Additionally, despite having more worms present, the juvenile monkeys had a strikingly lower type 2 immune response compared with the adult animals (21). However, the specific immunological mechanisms that control these age-dependent differences in the helminth-induced type 2 response are unknown.…”