scholarly journals Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): downregulation of specific cytokine secretion (IL-9 and IL-10) correlates with poor mastocytosis and chronic survival of adult worms

1993 ◽  
Vol 15 (7) ◽  
pp. 415-421 ◽  
Author(s):  
J. M. BEHNKE ◽  
F. N. WAHID ◽  
R. K. GRENCIS ◽  
K. J. ELSE ◽  
A. W. BEN-SMITH ◽  
...  
Parasitology ◽  
1989 ◽  
Vol 98 (3) ◽  
pp. 459-469 ◽  
Author(s):  
F. N. Wahid ◽  
M. Robinson ◽  
J. M Behnke

SUMMARYThe time-course of low and high intensity primary infections with Heligmosomoides polygyrus was monitored in SJL and SWR mice, both of which usually expel worms within 7 weeks of larval administration. Worm expulsion in these strains was not dependent on the intensity of infection, with low and high intensity worm burdens being lost within the same period of time. The ability to expel worms rapidly was inherited in a dominant manner in F1 offspring of SJL or SWR mice mated with C57Bl10 mice; the latter being a strain in which no loss of worms was evident within 10 weeks of infection. However, neither (SJL × C57Bl10)F1 nor (SWR × C57Bl10)F1 mice expelled worms as rapidly as the parental SJL and SWR strains. (SWR × B10G)F1 [H-2q] mice eliminated worms faster than (SWR × C57Bl10)F1 [H-2bq], suggesting that the b haplotype had a moderating influence on the expulsion process. In fact (SWR × B10G)F1 mice showed a significant reduction in worm burdens by week 4 but by weeks 6–8 the rate of worm loss had slowed considerably. In contrast, SJL and SWR mice, whilst initiating rejection slightly later, (after week 4) expelled all worms within the following 2 weeks. Thus two distinct patterns of response were observed among the fast responder strains as exemplified by SWR and SJL mice on the one hand and (SWR × B10G)F1 on the other. Our results support the hypothesis that the course of a primary infection with H. polygyrus is influenced by multiple host gene loci, some of which are encoded within the MHC. SJL and SWR mice probably have similar if not identical gene combinations at loci which determine a fast responder phenotype, distinguishing them from the other mouse strains which have been studied.


Parasitology ◽  
1987 ◽  
Vol 95 (3) ◽  
pp. 569-581 ◽  
Author(s):  
J. M. Behnke ◽  
Diane J. Williams ◽  
J. Hannah ◽  
D. I. Pritchard

SUMMARYChronic primary infections with Heligmosomoides polygyrus (Nematospiroides dubius) are still relatively poorly documented, particularly in relation to the role of host resistance in limiting worm survival. In the present work the duration of infection with H. polygyrus was studied in CFLP mice given doses of infective larvae ranging from 50 to 500 L3. The least heavily infected (50 L3) group ceased egg production earliest (week 36) whereas eggs were still detected in the faeces of mice given 500 larvae in week 42. At autopsy (week 42) mice given 50 larvae had virtually lost their entire worm burden with 5 out of 11 mice still harbouring a single worm each. However, all the mice in the group given 500 larvae were still infected, the highest worm burden being 93. The concentration of serum IgGl and specific antibody was highest in mice given 500 larvae, but sera taken from mice with declining worm burdens 19–38 weeks post-infection did not contain detectable host-protective antibody. During the course of infection in CFLP mice, H, polygyrus sustained irreversible changes in its capacity for subsequent survival. Thus, adult worms transferred to naive mice 2, 7, 14, 30 or 36 weeks post-infection did not live longer than worms of a comparable age in the respective donor group. In contrast, primary infection worms taken from jirds in which expulsion is usually completed by 6 weeks post-infection, re-established in mice and survived considerably longer than in the group of donor jirds. These results were discussed in relation to the possible interactions between parasite senility and immunomodulation, and host resistance in limiting primary infections with H. polygyrus in mice and jirds.


Parasitology ◽  
1991 ◽  
Vol 103 (1) ◽  
pp. 157-164 ◽  
Author(s):  
J. M. Behnke ◽  
F. N. Wahid

The course of primary infection was studied in BALB and B10 H-2 congenic mouse strains. The duration of infection, as assessed with regular faecal egg counts and worm burdens, was shorter in mice carrying the H-2s, H-2d or H-2q haplotypes when compared to mice with H-2b. Strains with H-2k were intermediate. An experiment was carried out to test the hypothesis proposed by Wassom, Krco & David (1987) predicting that the progeny of I–E+ve mouse strains crossed with I–E-ve strains, would show susceptibility rather than resistance to infection. This hypothesis was not substantiated by our data and we conclude that it does not apply to primary infections with Heligmosomoides polygyrus. It is proposed that the gene products of at least two loci within the H-2 (associated with the H-2b and H-2k haplotypes) are crucial in determining the response phenotype of mice to primary infection with H. polygyrus. One allele, (associated with the H-2b haplotype) may be preferentially affected by parasite-mediated immunosuppression.


Parasitology ◽  
1989 ◽  
Vol 98 (1) ◽  
pp. 115-124 ◽  
Author(s):  
M. Robinson ◽  
F. Wahid ◽  
J. M. Behnke ◽  
F. S. Gilbert

SummaryThe survival of Heligmosomoides polygyrus was monitored during primary infections in female C57Bl10, NIH and BALB/c mice at low and high intensities of infection. Survivorship curves were fitted for each data set and analysed. C57Bl10 mice, given either low or high intensities of infection, harboured parasites for 28–37 weeks, heavier infections surviving marginally but significantly longer. Essentially the survivorship curves of H. polygyrus in C57Bl10 mice could be accounted for by senility, the increased probability of worms with a longer life-span occurring at high infection intensities and, possibly, by a contribution from host-protective immune mechanisms in the terminal stages of infection. The pattern of survivorship was different in NIH and BALB/c mice. NIH mice showed weak but significant density-dependent suppression of parasite loss and infections in this strain did not exceed 27·5 weeks in duration. Primary infections in BALB/c mice were briefer still and showed marked dependence on parasite density. Thus low-level infections lasted 10–15 weeks whereas heavier infections survived for 21–34 weeks. The data suggested that both strains developed host-protective responses to adult H. polygyrus and that parasite survival was curtailed earlier than would be expected if senility alone was involved. The hybrid strains (C57Bl10 × NIH)F1 and (B10G × NIH)F1 both expelled H. polygyrus in a dose-dependent manner, worm loss commencing within 10 weeks of infection. In some experiments worm loss was clearly evident by weeks 4 and 6. These hybrid strains showed gene complementation in that adult worms were cleared considerably earlier than in parental strains.


1988 ◽  
Vol 62 (3) ◽  
pp. 221-231 ◽  
Author(s):  
M. Robinson ◽  
J. M. Behnke ◽  
D.J.L. Williams

ABSTRACTExperiments were carried out to explore the survival of 14-day adult H. polygyrus following transplantation to mice of four strains, immunized by various protocols. Adult worm establishment and survival was unimpaired in CFLP mice which were totally refractory to larval challenge. Transplanted adult worms were also successful in NIH mice immunized by the 9-day abbreviated infection regime. However, NIH mice exposed to irradiated larvae or subjected to the divided primary infection, expelled transplanted adults. The 9-day abbreviated infection was further examined in SJL and (C57 Bl10 X NIH) F1 mice which expel adult worms during a primary infection and although this regime was unsuccessful in causing NIH mice to reject adult worms, expulsion of adult worms was accelerated in SJL and F1 mice. The survival of adult H. polygyrus was discussed in the context of stage-specific immunity and the delicate balance between the immunogenic stimuli from developing larvae, the immunomodulatory activities of adult stages and the host's genetically determined capacity to respond to these opposing signals.


Parasitology ◽  
1983 ◽  
Vol 87 (1) ◽  
pp. 113-127 ◽  
Author(s):  
P. J. Brindley ◽  
C. Dobson

SUMMARYMice selected as liable (L) and refractory (R) over 10 generations voided significantly more and less Nematospiroides dubius eggs compared with randomly mated (Rd) mice after primary infection with 100 larvae. Strong positive correlation was found between the numbers of N. dubius eggs in mouse faeces and the numbers of adult N. dubius recovered from mice culled from the R, Rd and L colonies. Selection limit based on a faecal e.p.g. was reached in the L mice after 9 generations whereas the faecal N. dubius e.p.g. voided by the R mice continued to decline throughout selection. In contrast, no change in worm numbers was found in L or R mice after 6 generations. The refractory state of the trait, liability to infection with N. dubius, was inherited as a dominant character with a realized heritability value of ~ 0∣2. Differential correlated responses from N. dubius infectivity compared with N. dubius fecundity and growth indicated murine genetic control of this trait by 2 major genetic units. In general, there were negative phenotypic and genetic correlations between the faecal N. dubius e.p.g. of mice and murine morphological conformation, but positive correlations between the faecal N. dubius e.p.g. of selected mice and establishment, growth and fecundity of N. dubius populations in these mice. There was little correlation between the faecal N. dubius e.p.g. after primary infection and anti-N. dubius antibody titres and parasite female/male sex-ratio.


1982 ◽  
Vol 56 (4) ◽  
pp. 329-338 ◽  
Author(s):  
John Hannah ◽  
Jerzy M. Behnke

ABSTRACTThis project investigated the influence of the age and sex of the host and the level of infection with Nematospiroides dubius on the establishment and duration of a primary infection in the jird. It was found that 30 to 35% fewer worms matured in jirds than in mice and that this proportion was unaffected by the level of infection or by the sex of the host. In contrast the age of the jird was found to be critically important in determining the number of adult worms recovered 14 days after infection. Thus, maximum susceptibility to infection was observed when jirds were 18 to 22 days old. In older jirds susceptibility declined until 30 days after birth and thereafter, when approximately 70% of the infective larvae matured (relative to the number of worms maturing in mice).The duration of a primary infection in jirds was similar in both sexes but was influenced by the level of infection and by the age of the host at infection. Heavier infections (500 larvae) lasted about 10 days longer than low level infections, and expulsion of the parasite occurred even when the host was infected with only five larvae. The duration of a primary infection was markedly prolonged in neonatal jirds, faecal egg counts remaining positive for 54 to 56 days after infection of 12-day-old jirds.These results supply some further baseline data for future work on the biology of N. dubius in the jird and they provide support for the involvement of immunological processes in the termination of primary infections of this parasite in mature jirds.


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