To eliminate pathogens, the initiation of an appropriate immune response is critical. When the gastrointestinal nematode, Heligmosomoides polygyrus (Hp), invades the small intestine, a type-2 cytokine response is initiated; however, this response is not sufficient to clear the infection, and chronic infection can ensue. In this study, the host defense against Hp was investigated in mice with a focus on the role of CD4+ T cells. To this end, tissues from the small intestine and mesenteric lymph node (MLN) were collected every day from just after infection until Day 5 because many previous studies have described the later stages of infection from Day 8 to Day 12, during which Hp returns to the lumen and Th2 cytokine expression reaches its peak. In this study, we focused on investigating the initiation of the type-2 immune response. Our results indicated that the larvae encysted by Day 3. Increased type-2 cytokine gene expression started in the small intestine before Day 2 and increased again on Day 5. Interferon (IFN) γ increased significantly on the second day. Flow cytometry and gene expression analysis of MLN cells revealed that CD4+ T cells were not activated until Day 4. These results suggested that innate immune cells in submucosa are activated immediately after infection, but CD4+ T cells accumulate in the cyst zone later. In addition, IFNγ may have an important role in converting type-2 cytokine-producing cells from innate cells to CD4+ T cells.
Keywords: CD4+ T cell; mouse; nematode; small intestine; type-2 cytokine.