Immune Responses in Hookworm Infections

Abstract

Hookworms infect perhaps one-fifth of the entire human population, yet little is known about their interaction with our immune system. The two major species are Necator americanus, which is adapted to tropical conditions, and Ancylostoma duodenale, which predominates in more temperate zones. While having many common features, they also differ in several key aspects of their biology. Host immune responses are triggered by larval invasion of the skin, larval migration through the circulation and lungs, and worm establishment in the intestine, where adult worms feed on blood and mucosa while injecting various molecules that facilitate feeding and modulate host protective responses. Despite repeated exposure, protective immunity does not seem to develop in humans, so that infections occur in all age groups (depending on exposure patterns) and tend to be prolonged. Responses to both larval and adult worms have a characteristic T-helper type 2 profile, with activated mast cells in the gut mucosa, elevated levels of circulating immunoglobulin E, and eosinoophilia in the peripheral blood and local tissues, features also characteristic of type I hypersensitivity reactions. The longevity of adult hookworms is determined probably more by parasite genetics than by host immunity. However, many of the proteins released by the parasites seem to have immunomodulatory activity, presumably for self-protection. Advances in molecular biotechnology enable the identification and characterization of increasing numbers of these parasite molecules and should enhance our detailed understanding of the protective and pathogenetic mechanisms in hookworm infections

Purification and Molecular Cloning of and Immunization with Ancylostoma ceylanicum Excretory-Secretory Protein 2, an Immunoreactive Protein Produced by Adult Hookworms

“…Humans infected with hookworms typically produce parasite-specific humoral and cellular immune responses of the Th2 type (reviewed in reference 42). In contrast to the protective immunity in hamsters (as described above) and dogs (19,46), however, there is relatively little definitive evidence that natural protective immunity against hookworms develops in humans (6,42). Nevertheless, given that certain individuals appear to be predisposed to particular infection intensities (52,57), it would be interesting to examine AceES-2-specific immune responses in FIG.…”

The mucosal cellular response to infection withAncylostoma ceylanicum

“…The biology of these cell has been reviewed recently (Elphick & Mahida, 2005) and their numbers in crypts are believed to be controlled by a unique nonthymus-dependent mucosal T-cell population (Kamal et al, 2001). Hookworms are known to secrete a range of bioactive molecules, some of which are believed to play a role in their survival strategy in the face of the host immune system (Loukas & Prociv, 2001;Ghosh et al, 2006). One interpretation of our results is that among the secretions of A. ceylanicum are molecules that preferentially target this particular mucosal T-cell population, block its cytokines or interfere with cytokine receptors, in contrast to the thymus-derived, CD4þ helper cells that drive the type 2 responses (since mastocytosis and goblet cell hyperplasia were not downregulated).…”

Structure in parasite component communities in wild rodents: predictability, stability, associations and interactions .... or pure randomness?

“…As with all biological processes, however, there are some exceptions. Hookworms were able to survive the acute phase of the inflammatory response to T. spiralis in concurrently infected hamsters without any loss (Behnke, Rose and Little, 1994), a reflection of their remarkable resilience in the face of the host's immune response (Loukas and Prociv, 2001).…”