Chronic intestinal nematode infection induces Stat6-independent interleukin-5 production and causes eosinophilic inflammatory responses in mice.

The role of Stat6 (signal transducers and activators of transcription) in the recruitment and activation of eosinophils has been studied in detail in asthma and other allergic diseases. In this study, we demonstrated that eosinophil responses occur in a Stat6-independent manner in mice infected with the intestinal nematode, Nippostrongylus brasiliensis. Stat6-deficient (Stat6(-/-)) mice cannot expel N. brasiliensis and establish chronic infections. Prominent blood and intestinal eosinophilia were induced after day 14 postinfection (p.i.) and maintained at this level in Stat6(-/-) mice, whereas in wild-type mice eosinophil responses reached a peak on day 10 p.i. and declined thereafter. The introduction of a secondary infection of N. brasiliensis into wild-type mice induced rapid and exaggerated eosinophilia, whereas secondary infection in Stat6(-/-) mice resulted in almost the same eosinophil responses as those of the primary infection, suggesting a lack of memory responses. Blood eosinophilia was also induced in Stat6(-/-) mice implanted with N. brasiliensis in the small intestine, suggesting that intestinal exposure to parasitic antigen is sufficient to induce eosinophil responses. Furthermore, this prominent eosinophil response of Stat6(-/-) mice after day 14 was closely associated with an increase of interleukin (IL)-5 production in serum and intestine. Neither IL-4 nor eotaxin were significantly induced in Stat6(-/-) mice after infection with N. brasiliensis. We also found that mRNA for IL-5, GATA-3 and eosinophil peroxidase (EPO) are induced in the intestine of Stat6(-/-) mice on day 14 p.i. Taken together, these results provide evidence for Stat6-independent IL-5 production and subsequent eosinophil responses after chronic infection with N. brasiliensis.