Immunology of Ascaris suum in Pigs

Great progress has been made over the past 20 years in our understanding of the immune response to A. suum in pigs. Earlier studies showed that the inoculation of pigs with infective eggs was associated with the development of specific systemic IgG1, IgA, and IgM antibody responses,5,15 but that the predominant antibody secreting cells (ASC) in the mucosa of the proximal jejunum,5 duodenum,16 and bronchi16 were of the IgA isotype.5 That the immune response to A. suum in the pig is predominantly Th2 is reflected by an elevated peripheral blood eosinophilia,17,18 elevated frequencies of parasite-specific monocytes secreting IL-4 in peripheral blood and intestinal lymph nodes,18 and the increased expression of IL-4 in plasma and Th2 cytokines (e.g. IL-4 and IL-13) in the intestine19,20 and liver.21 An increased expression of IL-10 has been observed in the intestine and other tissues during infection19 where it may have a role in the regulation of inflammation.22

Resistance to A. suum in pigs has been observed following multiple oral infections with A. suum eggs,17,23,24 with radiation-attenuated A. suum eggs,25,26 and following immunization with parasite-derived products.27 Partial protection has also been achieved by giving colostrum from immunized sows28 and by passive transfer of hyperimmune sera.28 Protective immunity to A. suum in swine may occur in the liver, lungs, and in the intestine. Different infection or immunization strategies may have stronger effects on immunity generated in a particular tissue. A strong liver white-spot reaction, reflecting the host inflammatory response to the presence of the larvae in the liver, is a typical consequence of a secondary challenge exposure to infective eggs,29 although this reaction diminishes over time with trickle infections.24

Chronic natural and multiple inoculations with eggs has been associated with the development of pre-hepatic intestinal immunity29,30 while immunization with irradiated eggs or with A. suum antigens27,31 is associated with post-hepatic protective immunity. Relatively little is known of the specific immunological mechanisms by which protection is achieved. The intestinal expulsion of larvae that have migrated through the lungs has been associated with an increase in the frequency of intestinal mucosal ASCs producing parasite-specific IgA5 and with mast cell-mediated immediate hypersensitivity responses to parasite antigens.4,32 Non-specific immunological mechanisms may also have a role: pigs previously infected with transmissible gastroenteritis (TGE) virus were resistant to infection.33 Intestinal immunity to A. suum eggs does not appear to be directly related to the number of adult worms in the host because removal of adults by anthelmintic treatment or the direct transplantation into the intestine did not affect protective immunity following challenge with A. suum eggs.17

Immunology of Ascariasis in Humans

Chronic infections with A. lumbricoides in humans are associated with the production of high levels of specific and non-specific antibodies of all isotypes and IgG subclasses34,35 and a cytokine response characterized by the production of Th2 cytokines (i.e. IL-4, IL-13, and IL-5) by peripheral blood monocytes (PBMCs) and leukocytes (PBLs in whole blood cultures).36–38 Other Th2 effector responses are also prominent during infection, reflected by elevated numbers of peripheral blood eosinophils39 and increased expression of eosinophil degranulation products.10 The production of IFN-γ by PBMCs/PBLs stimulated with Ascaris antigens is not prominent in ascariasis37,38,40,41 but IL-10 production may be increased in infected individuals.37,42 An increased production of IL-10 has been observed also to occur spontaneously (i.e. in the absence of antigen stimulation) by PBMCs/PBLs of individuals with chronic infections,10,38 an observation previously made for other chronic helminth infections.43–45 Albendazole treatment of individuals co-infected with HIV and A. lumbricoides was associated with a decline in plasma IL-10 compared to co-infected individuals receiving placebo,46 providing further evidence that IL-10 may be upregulated non-specifically in infected individuals.

IL-10 is considered to be a key cytokine mediating immune regulation during chronic helminth infections10,38,43–45,47 and the combination of elevated Th2 cytokines with IL-10 has been referred to as a modified or regulated Th2 response.48,49 Another cytokine that has been associated with immune regulation during chronic helminth infections is TGF-β43: evidence for the increased expression of this cytokine during ascariasis is inconsistent with some studies suggesting increased production or expression of TGF-β134,47 but other authors have observed no such effect.10,41 It should be remembered that individuals living...