It may be that repeated infection in endemic areas is required for the stimulation of a TH1 response to hookworm; however, a study using repeated experimental infection (50 larvae followed by another 50 larvae 27 months later) showed negligible levels of IFN-γ to hookworm antigen at all time points (22). A further possibility is that other pathogens common in helminth endemic areas (e.g. malaria) may skew immune responses

towards a TH1 phenotype. In mouse models of coinfection with hookworm (Nippostrongylus brasiliensis) and TH1-inducing protozoa or bacteria, although a suppression of helminth-specific TH2 responses has been seen (32–34), to our knowledge, no induction of helminth-specific TH1 MAPK Inhibitor Library chemical structure responses has been reported in mice or humans. Thus, it is possible CP-673451 cell line that reports citing anti-hookworm IFN-γ responses are actually because of endotoxin contamination of the stimulating antigen, particularly given that adult and larval hookworms are derived from the intestine or faecal culture, respectively. This possibility is difficult to exclude without data from uninfected, unexposed control subjects, which is often absent from these studies. For instance, a recent study showed the highest production

of IFN-γ to larval antigens at week 0 of an experimental infection, prior to exposure to the parasite (25). Only a small number of studies have characterized the T- and B-cell immune response to hookworm ex vivo. Two studies show a small decrease in proportions of circulating CD4+ T cells and CD19+ B cells in hookworm-infected individuals from an endemic area (26,35), with increased levels of the activation markers CD69 and HLA-DR on T cells (26). Other studies have shown similar results with other parasitic (36) and bacterial (37,38) Etomidate infections, indicating this is most likely an effect of long-term inflammation, resulting in the activation of T cells and movement of T cells from the circulation to the effector site or draining lymph node. Hookworm infection also causes changes

to the cells of the innate immune system, most obviously blood eosinophilia. In both experimental and endemic infections, eosinophilia is evident within 4 weeks after exposure (7,8,22,25,39,40). Eosinophils from hookworm-infected individuals also show increased expression of activation markers compared to uninfected individuals (41). It is now recognized that eosinophils are competent antigen-presenting cells as well as effector cells, as they have been shown to process and present antigen on MHC class II molecules and stimulate T cells (42). Thus, eosinophils may be important cells in initiating or maintaining the immune response during hookworm infection. Recently, basophils have gained regard as a key cell type in TH2 immune responses.