Hookworms represent a major infectious burden globally, especially in developing countries. The murine hookworm Nippostrongylus brasiliensis is normally cleared in a manner dependent on IL-13, IL4-R and STAT6 signalling. Here we have used STAT6-deficient animals to model a non-resistant population and describe 2 novel STAT6-independent processes for the clearance of N. brasiliensis. During primary infection STAT6−/− animals are able to clear gut-dwelling N. brasiliensis by a mechanism involving the trapping and degradation of worms in the gut mucosa. Here, a previously undescribed STAT6-independent up-regulation of Relm-β was observed which correlated with the mucosal trapping and degradation of worms. Previous studies have indicated that during secondary infection STAT6 deficient animals fail to expel adult worms and remain susceptible to re-infection and long-term colonization of the gut. We report here that an initial partially protective response occurs early upon re-infection in the absence of STAT6, and that a late-phase protective secondary response arises in the gut of STAT6-deficient mice leading to the clearance of the majority of N. brasiliensis, through their trapping and death in the mucosal layer of the lower region of the small intestine. These findings show that there are a number of redundant effector pathways which act to reduce worm burden in the gut which can be activated by mechanisms that do not work through the dominant STAT6 signalling pathway and may be useful as targets for future vaccination strategies against resistant hookworm strains.

The subsets of lymphocytes and cytokines regulating the site-specific immune response in experimental cysticercosis (Taenia crassiceps) are not known. This study investigated the cells present at the site of infection (PECs) using flow cytometry and measured the cytokines produced by these cells through 50 days of infection. The results showed an expansion of B220+CD5+, B220+CD5−, αβTCR+CD4+ and CD8+ cells coincident with a transient increase in IL-10 production. After the initial increase, the percentage of B220+ CD5− and helper T cells decreased with a concomitant decrease in IL-10 production. CD8+ T cells continued to increase throughout infection and γδTCR+ cells increased after 10 days of infection. PECs demonstrated an increased IFN-γ and IL-4 production throughout infection when stimulated with larval antigens. Because a Th2-type polarization has been shown for spleen cells from infected BALB/c mice, cytokine profiles of spleen cells and PECs in response to ConA and larval antigens were compared. ConA and antigen-specific stimulation of spleen cells from 50-day-infected mice produced increased amounts of IL-10 while PECs showed a decreased IL-10 production suggesting that anatomically distinct lymphoid populations produce different cytokines and promote different types of responses. Surprisingly, late in infection the levels of IL-4 and IFN-γ in serum increased substantially (460-fold and 100-fold, respectively). The systemic immune response of BALB/c mice during experimental cysticercosis, therefore, is a mixed Th1/Th2-type response.