The relative involvement of Th1 and Th2 associated immune responses in the expulsion of a primary infection of Heligmosomoides polygyrus in mice of differing response phenotype

Abstract

T helper cell (Th1 and Th2) associated responses were examined following a primary infection with the gastrointestinal nematode Heligmosomoides polygyrus in five inbred strains of mice with different resistance phenotypes. Levels of (i) mast cell protease, (ii) specific IgE, (iii) nitric oxide and (iv) specific IgG2a, as markers of Th2 and Th1 associated responses, respectively, were determined in sera and intestinal fluids and correlated with worm burdens. The 'fast' responder (resistant) strains SWR and SJL produced strong Th2 and Th1 associated responses respectively in a mutually exclusive fashion. The F 1 hybrid (SWR £ SJL) F 1 , showed rapid expulsion of the parasite and expressed both intense Th1 and Th2 responses, suggesting synergism between Th1 and Th2 activity in these mice. The results indicate that both Th2 and Th1 responses operate in mice following a primary infection with H. polygyrus and that each Th response may be involved to a greater or lesser degree within certain strains. Resistance to H. polygyrus was found to correlate only to the intensity of either the gut-associated mastocytosis or nitric oxide production in these strains but not to either specific IgE or IgG2a titres. Chronic infections in the 'slow' response phenotype mouse strains CBA and C57BL/10, were associated with both poor Th2 and poor Th1-associated responses attributed to a general parasite-mediated immunosuppression of the host immune response to infection.

Immunity to the model intestinal helminth parasite Heligmosomoides polygyrus

“…Specifically, the IgG1 and IgE responses (to adult worm homogenate and HES) negatively correlate across strains with worm survival after a primary infection [12, 51, 52]. However, after repeated low-dose (“trickle”) infections, there was little difference between slow and fast responder strains in any antibody isotype measured to larval and worm antigens [53].…”

“…Mast cells are major players in the intestinal immune response to infection with H. polygyrus , as expulsion correlates with epithelial mastocytosis [52, 96] and elevated intestinal fluid levels of mMCP-1 in different murine strains [51]. Mast cells may promote helminth damage by increasing the permeability of the gut via mMCP-1-mediated breakdown of epithelial tight junction proteins [97, 98], thereby increasing luminal flow and disrupting the niche of parasitic helminths.…”

Hookworm virulence factors: making the most of the host

“…The elimination of parasitic helminths varies according to the species and is achieved through the activation of two pathways regulated by distinct CD4 þ Th cell populations [97]. The first pathway is characterized by an acute immediate hypersensitivity type inflammatory response associated with mucosal mastocytosis through Th2 cells that is coordinated by IL-3, IL-4, IL-9 and IL-10 cytokines which result in eosinophilia, mucus secretion by goblet cells, intestinal epithelial cell function and specific IgE production.…”

“…The first pathway is characterized by an acute immediate hypersensitivity type inflammatory response associated with mucosal mastocytosis through Th2 cells that is coordinated by IL-3, IL-4, IL-9 and IL-10 cytokines which result in eosinophilia, mucus secretion by goblet cells, intestinal epithelial cell function and specific IgE production. The second pathway is associated with the Th1 arm of the immune response and is characterized by a delayed type hypersensitivity/cell-mediated immune reaction, involving macrophage activation, cytotoxic T cells, and NK cell antibody-dependent cytotoxicity, increased epithelial cell turnover, and specific IgG2a production [97].…”

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

“…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.…”