Differential resistance to nematode infection is associated with the genotype- and age-dependent pace of intestinal T cell homing.

The resistance of inbred mice to nematode infections varies depending on the extent of protective Th2 responses. Here, we compared two mouse lines differing in resistance to infection with the enteric nematode Heligmosomoides polygyrus bakeri despite the similar instruction of GATA-3+ T effector cells. Resistant BALB/c mice rapidly recruited high numbers of Th2 cells to the gut within the 1-week time frame required for larval development in the intestinal submucosa. C57BL/6 mice failed in the optimal control of early nematode fitness, with mucosal Th2 response peaking after 2 weeks when the larvae had left the tissue and relocated to the gut lumen as adult worms. The faster homing of Th2 cells to the gut of BALB/c mice is related to the extensive expression of the chemokine receptor CCR9 in GATA-3+ cells and higher frequencies of aldehyde dehydrogenase expressing dendritic cells present in mesenteric lymph nodes. Furthermore, nematode-infected older BALB/c mice displayed impaired resistance due to delayed mucosal homing of effector cells, which synergized with more numerous Th2/1 hybrid cells acting as IFN-γ-dependent confounders of type 2 responses. Hence, the distinct kinetics of effector cell recruitment to the infected gut and the quality of GATA-3+ T cell responses contribute to the genotype- and age-dependent resistance to intestinal nematode infections.