T-helper-1 and T-helper-2 immune responses in mice infected with the intestinal fluke Neodiplostomum seoulense: their possible roles in worm expulsion and host fatality.

Neodiplostomum seoulense is highly pathogenic and lethal to experimental mice; most worms are expelled within 2 mo of acquisition. In this study, T-helper (Th) cell immune responses were studied in N. seoulense-infected BALB/c mice. Spleen and mesenteric lymph node (MLN) cells of infected mice proliferated in response to parasite antigens; CD4+ T cells proliferated more than CD8+ T cells. Antigen-induced interferon (IFN)-gamma (a Th1 cytokine) secretion began to increase at day 7 postinfection (PI) in spleen and MLN cells, and this was maintained at day 28 PI, whereas interleukin (IL)-4 (a Th2 cytokine) secretion was somewhat lower. Similar results were observed for mRNA signals of IFN-gamma and IL-4. Antigen-specific serum total immunoglobulin (Ig)G, IgG1, IgM, and IgA levels (Th2-induced) were elevated from days 7 to 14 to day 28 PI, and IgG2a (Th1-induced) was elevated at days 21 to 28 PI. Interestingly, the numbers of macrophages (Th1- or Th2-induced), which were found to kill N. seoulense worms in vitro, increased remarkably during days 14-28 PI in spleens and small intestines of infected mice. This study shows that mixed Th1 and Th2 responses occur during the course of N. seoulense infection in BALB/c mice. Heavy infiltrations of macrophages in the small intestine may participate in host damage and worm expulsion.