Immunity against helminths: interactions with the host and the intercurrent infections

Abstract

Helminth parasites are of considerable medical and economic importance. Studies of the immune response against helminths are of great interest in understanding interactions between the host immune system and parasites. Effector immune mechanisms against tissue-dwelling helminths and helminths localized in the lumen of organs, and their regulation, are reviewed. Helminth infections are characterized by an association of Th2-like and Treg responses. Worms are able to persist in the host and are mainly responsible for chronic infection despite a strong immune response developed by the parasitized host. Two types of protection against the parasite, namely, premune and partial immunities, have been described. Immune responses against helminths can also participate in pathogenesis. Th2/Treg-like immunomodulation allows the survival of both host and parasite by controlling immunopathologic disorders and parasite persistence. Consequences of the modified Th2-like responses on co-infection, vaccination, and inflammatory diseases are discussed.

Figure 1

Immune mechanisms and regulation induced against Fasciola hepatica. Two main immune mechanisms are directed against F. hepatica in the liver parenchyma: (i) during the early phase of infection, classically activated macrophages may induce nitric oxide production which is toxic for the fluke. This mechanism needs to be confirmed and may be upregulated by Th1-type cytokines and downregulated by IL-10 produced by T regulatory cells. (ii) During the chronic phase of infection, antibody-dependent cellular cytotoxicity (ADCC) allows the release of toxic mediators such as major basic protein, eosinophil cationic protein, and reactive nitrogen intermediates. This mechanism is upregulated by Th2-type cytokines. T regulatory cells (Treg cells) produce IL-10 TGFβ which inhibit the production and function of Th1 cytokines. They downregulate any excessive Th2 response in the immunopathogenesis of fasciolosis. Finally, alternative activated macrophage (AAMϕ) produces molecules that are toxic to the fluke and participates in fibrosis and tissue repair.

Figure 2

Main evasion mechanisms developed by Fasciola spp. against ADCC. Three main evasion mechanisms have been described: (i) production of superoxide dismutase and Glutathione S-transferase which neutralize superoxide radicals, (ii) cleavage of IgE and IgG involved in the ADCC, and (iii) production of blocking antibodies IgM and IgG2 which could inhibit eosinophil adhesion to flukes.

Figure 3

Immune response against gastrointestinal nematodes (GNE: eosinophil granulocyte, HS1: type 1 hypersensitivity). Against larva, ADCC and type 1 hypersensitivity are involved to block their migration in gut mucosa and to eliminate the parasite. Against adult in the lumen of gut, intestinal anaphylaxis responsible for muscle contractility, mucus secretion, and so forth, leads to the expulsion of the parasite. IgA neutralizes the metabolic enzymes and interferes with the worm's ability to feed.