Genetic variation in resistance to repeated infections with Heligmosomoides polygyrus bakeri, in inbred mouse strains selected for the mouse genome project

Abstract

Since the publication of the mouse genome, attention has focused on the strains that were selected for sequencing. In this paper we report the results of experiments that characterized the response to infection with the murine gastrointestinal nematode Heligmosomoides polygyrus of eight new strains (A/J, C57BL/6, C3H, DBA/2, BALB/c, NIH, SJL and 129/J), in addition to the well-characterized CBA (poor responder) and SWR (strong responder) as our controls. We employed the repeated infection protocol (consisting of 7 superimposed doses of 125L3 each administered at weekly intervals, faecal egg counts in weeks 2, 4 and 6 and assessment of worm burdens in week 6) that was used successfully to identify quantitative trait loci for genes involved in resistance to H. polygyrus. SWR, SJL and NIH mice performed indistinguishably and are confirmed as strong responder strains to H. polygyrus. CBA, C3H and A/J mice all tolerated heavy infections and are assessed as poor responders. In contrast, DBA/2, 129/J and BALB/c mice performed variably between experiments, some tolerating heavy worm burdens comparable to those in poor responders, and some showing evidence of resistance, although only in one experiment with female 129/J females and one with female BALB/c was the pattern and extent of worm loss much like that in SWR mice. Because the genetic relationships between six of the strains exploited in this study are now well-understood, our results should enable analysis through single nucleotide polymorphisms and thereby provide more insight into the role of the genes that control resistance to H. polygyrus.

Effects of protein malnutrition on tolerance to helminth infection

“…In laboratory mice, H. polygyrus infection may lead to impaired growth and occasionally mortality [11,12]. Strains like C3H or CBA maintain high parasite loads for more than 20 weeks, whereas loads are lower and parasites more rapidly cleared in, for example, SWR and BALB/c mice [13,14], indicating genetic variation for resistance. Protein malnutrition compromises Th2-mediated immunity to H. polygyrus, and thereby reduces resistance [5].…”

Trichinella spiralis reinfection: changes in cellular and humoral immune response in BALB/c mice

“…This may lead to strong resistance to reinfection (Wakelin, 1993). It is also known that there are differences in immunity during primary and challenge parasitic infections between host species or even among inbred mice strains which varied genetically (Behnke et al, 2006). Trichinella spiralis is the intestinal nematode parasite with worldwide distribution and which causes trichinellosis -a serious zoonosis.…”

“…Muscle infection with T. spiralis elicited a chronic infection where a major role in host defense processes is played by cellular immunity (Mahida, 2003). Larvae survive in nurse cells in close association with macrophages, CD8+ and CD4+ T lymphocytes, and B lymphocytes (Beiting et al, 2004). B lymphocytes secreting antibodies, particularly IgG and IgE, may lead to an effecttive antibody-dependent cell mediated cytotoxic reaction against T. spiralis newborn larvae (Moloney & Denham, 1979;Wang & Bell, 1988;Dvorožňáková et al, 2010).…”

Submitted summaries

“…Here, we aim to identify a mouse model to scientifically evaluate the suitability of plant preparations for parasite control. Whilst between-strain variation in nematode resistance is well described (Behnke et al, 2006), there is no evidence of between-strain variation in nematode resilience. This needs to be demonstrated, as mice will serve as model organisms for livestock, which experience performance penalties during parasitism.…”

“…C57BL/6, BALB/c and NIH, characterized as having high, intermediate and low susceptibility to infection with the nematode Heligmosomoides bakeri as defined by their phenotype (Behnke et al, 2006). Mice (male, 6 weeks of age) were either parasitized with a single dose of 250 L 3 H. bakeri (P; n=10) in water or were sham-infected with water (C; n=10), as per previously established model (Coltherd et al, 2011).…”