Molecular mechanisms of hookworm disease: Stealth, virulence, and vaccines

• Published in: Journal of allergy and clinical immunology 2012-07, Vol.130 (1), p.13-21
• Main Authors: Pearson, Mark S., PhD, Tribolet, Leon, BSc, Cantacessi, Cinzia, PhD, Periago, Maria Victoria, PhD, Valerio, Maria Adela, PhD, Jariwala, Amar R., MD, Hotez, Peter, MD, PhD, Diemert, David, MD, Loukas, Alex, PhD, Bethony, Jeffrey, PhD
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Ancylostoma secreted proteins; Ancylostomatoidea - genetics; Ancylostomatoidea - metabolism; Ancylostomatoidea - pathogenicity; Ancylostomatoidea - physiology; Ancylostomiases; Anemia, Iron-Deficiency - immunology; Anemia, Iron-Deficiency - parasitology; Animals; Antigens, Helminth - genetics; Antigens, Helminth - immunology; Antigens, Helminth - metabolism; Biological and medical sciences; Disease; Diseases caused by nematodes; Enzymes; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Helminth Proteins - genetics; Helminth Proteins - metabolism; Helminthic diseases; Hookworm Infections - immunology; Hookworm Infections - parasitology; Hookworm Infections - physiopathology; Hookworm Infections - prevention & control; Hookworms; Humans; immune modulation; Immunopathology; Infections; Infectious diseases; Malnutrition; Medical sciences; Parasites; Parasitic diseases; Pathogenesis; proteases; Proteins; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Skin; Tropical diseases; vaccines; Vaccines - immunology; Virulence; virulence factors
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2012.05.029

Hookworms produce a vast repertoire of structurally and functionally diverse molecules that mediate their long-term survival and pathogenesis within a human host. Many of these molecules are secreted by the parasite, after which they interact with critical components of host biology, including processes that are key to host survival. The most important of these interactions is the hookworm’s interruption of nutrient acquisition by the host through its ingestion and digestion of host blood. This results in iron deficiency and eventually the microcytic hypochromic anemia or iron deficiency anemia that is the clinical hallmark of hookworm infection. Other molecular mechanisms of hookworm infection cause a systematic suppression of the host immune response to both the parasite and to bystander antigens (eg, vaccines or allergens). This is achieved by a series of molecules that assist the parasite in the stealthy evasion of the host immune response. This review will summarize the current knowledge of the molecular mechanisms used by hookworms to survive for extended periods in the human host (up to 7 years or longer) and examine the pivotal contributions of these molecular mechanisms to chronic hookworm parasitism and host clinical outcomes.