Muris

This material is based upon work supported by the Army Research Office through a MURI grant (DAAD19-03-1-0169) for fuel ceU research to the Case Western Reserve University by the Army Research Office under award Army W91 lNF-08-1-0309, by the National Science Foundation under awards DMR 0504038 and NSF CHE06-51083, and by the Air Force Office of Scientific Research under award FA9550-06-1-0235. 

Harris M.A. and Murie J.O. (1984). Discrimination of estrous status by Columbian Ground Squirrels. Anim Behav 32, 939-940. 

There is good evidence, for a number of helminth species, that different parasite lines vary in their infection characteristics in hosts, much of which is reviewed by Read and Viney (1996). For example, different isolates of Trichinella spiralis vary in the kinetics of their primary infection in the same mouse strain. Crucially, these differences are removed when mice are immunosuppressed (Bolas-Fernandez and Wakelin, 1989). Analogous observations have been made for Trichuris muris in mice. Different isolates differed in the kinetics of infection and expulsion. However, in immunosuppressed mice, all isolates had similar fecundity (Bellaby et al., 1995). Combined, these observations show immune-dependent variation between parasite lines in their infection kinetics. 

Bellaby, T., Robinson, K., Wakelin, D. and Behnke, J.M. (1995) Isolates of Trichuris muris vary in their ability to elicit protective immune responses to infection in mice. Parasitology 111, 353-357. 

A critical and IL-4-independent role for IL-13 has also been identified in host resistance to T. muris. Despite generating strong and equivalent type 2 responses to wild-type mice, mice deficient in IL-13 production failed to clear infection (Bancroft et al., 1998). Expulsion in BALB/c IL-4 KO mice was completely blocked following treatment with A25, confirming an important role for IL-13 in resistance to 1. muris (A.J. Bancroft et al., unpublished observations) (Table 17.1). In addition, IL-4 receptor KO mice (lacking IL-4 and IL-13 functions) are completely susceptible to T. muris (A.J. Bancroft, unpublished observations). 

Table 17.1. Mean worm burdens in IL-13 knockout (KO), IL-4 KO and wild-type mice at day 35 post-Trichuris muris infection.

Fig. 17.1. T reatment of normally resistant BALB/c IL-4 KO mice with anti-TNF-a monoclonal antibody prevents IL-13-mediated expulsion of T. muris. Mice were infected on day 0 with 200 T. muris eggs and worm burdens (+ sem) from four mice per group determined on days 18, 22 and 35 post-infection. (Data adapted from Artis etal., 1999a.)...

Fig. 17.2. (Opposite) Immuno-gold localization of a T. muris-derived IFN-y homologue to the bacillary band and cuticular pore. (A) Transmission electron micrograph of bacillary band showing the pore chamber (PC), pore aperture (PA) and lamellar apparatus (LA) (x22,000). (B) High-power localization of antibody staining (black dots) to the lamellar apparatus (LA) and pore chamber (PC) (x36,000). (Courtesy ofF. Bughdadi.)...

As mentioned above, yS T cells are numerous in the gut and can produce cytokines in the absence of conventionally presented antigen (Kaufmann, 1996). These cells have been shown to produce IL-4 or IFN-y (Ferrick el al., 1995) and are potentially an important source of these cytokines in the intestinal microenvironment following nematode infection. Supporting this suggestion, IL-4 mRNA has been found in y8 T cells from the caecum of resistant mice immediately following T. muris infection (Lukaszewski and R.K. Grencis, unpublished observations). 

Mast cells do not appear to play a direct role in host protection against primary T. muris infection, as no correlation was found between intestinal... 

Eosinophilia is a hallmark of intestinal nematode infection and is known to be under the control of IL-5 (Finkelman et al., 1992). As discussed above, treatment with anti-IL-5 monoclonal antibody (and so ablation of eosinophilia) had no effect on expulsion of T. muris, 77. polygyms, N. brasiliensis or T. spiralis infections, suggesting that either redundant mechanisms operate under these circumstances or that eosinophils are not a critical component of effector responses operating against most murine... 

It is clear from studies in the 7. muris, H. polygyrus and N. brasiliensis systems that administration of IL-4C to infected SCID mice can mediate... 

It is the quality rather than the quantity of the goblet cell response that is important in resistance to nematode infection, as even strains that are susceptible to I. muris (harbouring chronic infections) have a dramatic increase in the number of goblet cells and amount of mucus secreted during infection. Indeed, detailed analysis of the biochemical nature of... 

T cell and cytokine regulation of enterocyte apoptosis may also be important in the expulsion of nematodes, in particular T. spiralis and T. muris, which inhabit an intracellular niche. Certainly an increase in the number of apoptotic cells within the epithelium is observed around the period of expulsion of T. muris in resistant mouse strains (D. Artis, C.S. Potten and R.K. Grencis, unpublished). Apoptosis of host enterocytes may dislodge the nematode or perhaps expose vital feeding organs to immune attack, and so enhance expulsion. Whether enterocyte apoptosis results from the burrowing action of the worms or a tissue repair mechanism, or is involved in expulsion, remains to be investigated. 

Artis, D., Potten, C.S., Else, K.J., Finkelman, F.D. and Grencis, R.K. (1999b) Trichuris muris. host intestinal epithelial cell hyperproliferation during chronic infection is regulated by interferon-y. Experimental Parasitology 92, 144-153. 

Betts, C.J. and Else, K.J. (1999) Mast cells, eosinophils, and antibody-mediated-cellular-cytotoxicity are not critical in resistance to Trichuris muris. Parasite Immunology 21, 45-52. 

Else, K.J. and Wakelin, D. (1988) The effects of H-2 and non H-2 genes on the expulsion of the nematode Trichuris muris from inbred and congenic mice. Parasitology 96, 543-550. 

Else, KJ. and Wakelin, D. (1989) Genetic variation in the humoral immune response of mice to the nematode Trichuris muris. Parasite Immunology 11, 77-90. 

Else, K.J., Wakelin, D. and Roach, T.I.A. (1989) Host predisposition to trichuriasis the mouse-T. muris model. Parasitology 98, 275-282. 

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