Immunopathology and modulation induced by hookworms: From understanding to intervention

Abstract

Hookworm infection is considered the most prevalent human soil‐transmitted helminth infection affecting approximately 500 million people and accounting for 3.2 million disability‐adjusted life years lost annually. As with many other neglected tropical diseases, no international surveillance mechanisms that show accurate data on the prevalence of hookworm infection are in place, thus hindering strategies to control parasite transmission. In this review, we unravel the current knowledge in immunopathology and immunoregulation of hookworm infection and present discoveries in drug therapies based on the capability of hookworms to regulate inflammation to treat allergic, inflammatory and metabolic diseases. Additionally, we highlight potential vaccine development and treatments and propose avenues for further inquiry.

An efficient method for viable cryopreservation of hookworms and other gastrointestinal nematodes in the laboratory

“…Its prevalence is rapidly spreading, along with a multidrug resistant phenotype, making it increasingly recalcitrant to treatment (Jimenez Castro et al 2021, 2020). Development of new and better therapies and a protective hookworm vaccine are considered important goals for global and animal health (Loukas, Maizels, and Hotez 2021; Haldeman, Nolan, and Ng’habi 2020; Shepherd, Wangchuk, and Loukas 2018; Mourão Dias Magalhães et al 2021; Hu, Nguyen, et al 2018; Noon et al 2019).…”

“…The pressure imposed by parasitic worms on human genes has been hypothesized to be stronger than that of viral, protozoa, or bacterial agents (Fumagalli et al 2011). Because of their strong immunomodulatory characteristic, hookworms, most notably Necator americanus , and their secreted products are garnering great interest for treatment of autoimmune and autoinflammatory diseases such as celiac disease, asthma, metabolic syndrome, multiple sclerosis, and inflammatory bowel diseases (Loukas, Maizels, and Hotez 2021; Mourão Dias Magalhães et al 2021; Loukas et al 2016; Montaño, Cuéllar, and Sotillo 2021; Ryan et al 2020; Chapman et al 2021).…”

“…Development of new and better therapies and a protective hookworm vaccine are considered important goals for global and animal health (Loukas, Maizels, and Hotez 2021;Haldeman, Nolan, and Ng'habi 2020;Shepherd, Wangchuk, and Loukas 2018;Mourão Dias Magalhães et al 2021;Hu, Nguyen, et al 2018;Noon et al 2019).…”

Parasites and tissue microenvironment

“…In this issue, Mourão Dias Magalhães. et al 5 review the immune response generated against intestinal hookworm infection, with a particular focus on the immunomodulatory capacity of such organisms, as well as the prospect of a vaccine. Multiple studies aimed at understanding the immunomodulatory mechanisms of helminths have provided support for the ability of hookworms to modulate inflammation, thus allowing the exploration of the use of live parasitic worms, worm secretions, and worm‐derived synthetic molecules to treat various allergic, inflammatory, autoimmune, and metabolic diseases.…”