Enhanced Protection against Heligmosomoides polygyrus in IL-2 Receptor .BETA.-Chain Overexpressed Transgenic Mice with Intestinal Mastocytosis

Abstract

ABSTRACT. IL-2 receptor -chain overexpressed transgenic (Tg2R) mice lack NK cells, but the development of other lymphocyte subsets and macrophages remained apparently intact. These mice also exhibit intestinal mastocytosis. Helminth infection induces various immune responses, such as mast cells, goblet cells, eosinophils and IgE, mediated by Th2 cytokines. IL-4 is also important in the regulation of resistance and susceptibility to Heligmosomoides polygyrus infection. However, there are contradictory results about the relation between resistance to H. polygyrus and intestinal mastocytosis. The present study showed that Tg2R mice suppressed worm fecundity with mastocytosis without an increase of the levels of goblet cells, eosinophils and IgE compared with control mice. These results clearly indicated that mast cells have the ability for to protect against H. polygyrus infection. However, additional studies are required to evaluate protective effector mechanisms against H. polygyrus. IL-2 receptor -chain overexpressed transgenic (Tg2R) mice lack NK cells, but the development of other lymphocyte subsets and macrophages remained apparently intact [14]. We found that Tg2R mice represent intestinal mastocytosis and globule leukocytes without any inflammation in a normal state (Fig. 1). Although the mechanisms of mast cell hypertrophy and the relationship of NK cell deficiency and mast cell increment have been unknown in this transgenic mouse, this is the only mouse that represents intestinal mastocytosis without any pathological stimuli. So, this transgenic mouse is a useful animal model for investigating mast cell function. Helminth infections induce various immune responses such as marked IgE antibody production, peripheral blood eosinophilia, intestinal mucosal mastocytosis and a hyperplasia of intestinal goblet cells, and these immunological responses have the protective effects against helminth [4,7,8]. However, protection against each parasite is through considerably different mechanisms [3,6]. Contradictory results have been reported about the relation between resistance to Heligmosomoides polygyrus and intestinal mastocytosis [1, 2, 5], and the specific effector mechanisms mediating worm expulsion remain unknown [1,15]. In the present study, we investigated the protective ability against H. polygyrus of Tg2R mice, in which mast cells are increased without inflammation.To obtain Tg2R mice, male Tg2R and female C57BL/ 6J (B6) were mated, and each offspring was verified to be a transgenic mouse by a PCR method, as described previously [10,14]. Transgenic and wild-type litter mate mice were used. Autoclaved pellets (MF; Oriental Yeast, Tokyo, Japan) and water were supplied ad libitum. All animals were handled under the regulations for animal welfare of Yamaguchi University. Groups of more than five mice of the same age and approximately the same weight were used for each experiment. H. polygyrus was maintained by serial passage in mice, as described previously [9]. Both groups of mice were inoculated ora...

Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus

“…During H. polygyrus infections, these mice produce higher egg numbers than wild-type controls, indicative of impaired immunity [100]. Consistent with this, reduced egg production was seen in Tg2Rbeta mice [101], which exhibit mastocytosis.…”

Susceptibility and immunity to helminth parasites

“…In tissue infections, progressive calcification of adult worms can occur, depriving parasites of surface nutrient exchange. In this respect, it can be noted that while no single cell subset is responsible for this type of attack, a number of transgenic overexpression models report that elevated mast cell [37] or eosinophil [38] responses are able to exert strong anti-parasite effects, while nitric oxide from macrophages and neutrophils can harm tissue larvae [39]. Hence, in physiological settings it is likely that multiple cell types contribute incrementally to damaging parasites.…”

Immune modulation and modulators in Heligmosomoides polygyrus infection

“…In contrast, antibody-mediated depletion of IL-5 and consequent ablation of eosinophilia, has no effect on worm explusion following secondary infection (Urban, et al, 1991). A role for mast cells in primary immunity was suggested as IL-9 overexpressing transgenic mice are able to clear the infection, and this was associated with their high levels of mucosal mast cells (Hayes, et al, 2004, Morimoto and Utsumiya, 2011).…”