Hookworms survive for several years in the host lumen, inducing a robust but ineffective immune response. While the role of the adaptive response in human helminth infection has been well investigated, the role of the innate immune responses remains to be elucidated. We report on the development of dendritic cells (DCs) and the role of eosinophils during human hookworm infection. DCs from hookworm-infected individuals did not mature in the same manner as DCs from non-infected volunteers. Additionally, hookworm-infected individuals have lower expression of costimulatory (CD86) and antigen presenting molecules (CD1a, HLA-ABC, HLA-DR), which was coincident with a reduced ability of the DCs to induce cell proliferation. We also showed that this alternative DC differentiation is partially induced by excreted-secreted hookworm products. Conversely, eosinophils from the same individuals showed a highly activated status, with an upregulation of major cell surface markers. Moreover, eosinophils from hookworm-infected individuals induced a significant cell proliferation to crude antigen extracts compared to non-infected individuals. We show that, while hookworm infection modulates the development of DCs, the major cell surface markers of eosinophils are upregulated. Our data suggest that hookworm infection may alter the host's innate immune response, resulting in parasite-impaired DCs and activated, antigen presenting eosinophils.