The Immune Response to Nematode Infection

Abstract

Nematode infection is a major threat to the health of humans, domestic animals and wildlife. Nematodes vary in their effect on the host and in the mechanisms underlying immunity but the general features are becoming clear. There is considerable variation among individuals in resistance to infection and much of this variation is due to genetic variation in the immune response. The major histocompatibility complex has a strong influence on resistance to infection but other genes are collectively more important. Resistant individuals produce more IgA, eosinophils, IgE and mast cells than susceptible individuals and this is a consequence of stronger type 2 (Th2) immune responses. A variety of factors promote Th2 responses including genetic background, diet, molecules produced by the parasite and the location of the infection. A variety of cells and molecules including proteins, glycolipids and RNA act in concert to promote responses and to regulate the response. Nematodes themselves also modulate the host response and over 20 parasite-derived immunomodulatory molecules have been identified. Different species of nematodes modulate the immune response in different ways and probably use multiple molecules. The reasons for this are unclear and the interactions among immunomodulators have still to be investigated.

Mucosal Immunity of Major Gastrointestinal Nematode Infections in Small Ruminants Can Be Harnessed to Develop New Prevention Strategies

“…Columbianum, T. colubriformis, and H. contortus in sheep; A. caninum in dogs; and Trichinella spiralis in pigs, with varying levels of success as summarised in Table 1. Nematodes are large extracellular parasites with complex genomes that are required for escaping various immune responses for successful establishment in the host [37]. An effective vaccine would need to stimulate many different host immune pathways to sufficiently survive subsequent infection.…”

“…The development of immune competence primarily occurs through the prevention of the establishment of newly ingested larvae within the gastrointestinal tract, suppression of parasite growth, expulsion of adult worms, or a combination of all three mechanisms [34,35]. Immunity to intestinal worms also develops more rapidly when compared to abomasal worms [36,37]. It has also been shown that immune responses against GINs in small ruminants is different in sheep when compared to goats [38].…”

“…Protective Th2 responses are common during helminth parasitic infections [45]. Production of specific cytokines (IL-3, IL-4, IL-5, IL-9, and IL-13), along with the infiltration of eosinophils, basophils, mast cells, and IgE production, are the main features of protective Th2 immune responses to GIN infections [37,63,64]. On the other hand, an increased proliferation of Th1 effector molecules is associated with susceptibility to GIN infection [65,66].…”

“…Shifting Th2 towards Th1 immune responses by using IL-12 gene transfer was shown to significantly change T. spiralis infections in mice by prolonging worm survival and inhibiting muscle hypercontractility along with goblet cell hyperplasia [68]. Additional studies on helminth infection have identified group 2 innate lymphoid cells (ILC2s) as a major component of type Th2 innate responses to infections responsible for IL-5 and IL-3 secretion that induce goblet cell division, increase in mucus secretion, smooth muscle contraction, eosinophil and mast cell recruitment and alternative macrophage activation [37,64,69].…”

Helminth Lessons in Inflammatory Bowel Diseases (IBD)

“…grade Necator americanus (hookworm) infection in the rural United States [4], only causes a self-limited colonization with no overt pathology. Helminth infections trigger an immune response in their mammalian hosts but are often able to regulate that response to promote the survival of the parasite and suppress expulsion, although a comprehensive understanding of the mechanism of the latter is lacking [5]. Helminthic regulation or immunity is clearly beneficial for the parasite, but as we will see throughout this review, the induction of immune regulatory pathways can have favorable effects on the host and the host's immune function (Figures 1 and 2).…”