scholarly journals 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

2003 ◽  
Vol 77 (2) ◽  
pp. 133-146 ◽  
Author(s):  
A. Ben-Smith ◽  
D.A. Lammas ◽  
J.M. Behnke
Keyword(s):  
Nitric Oxide ◽  
Primary Infection ◽  
Gastrointestinal Nematode ◽  
Inbred Strains ◽  
Specific Ige ◽  
Mouse Strains ◽  
Chronic Infections ◽  
Heligmosomoides Polygyrus ◽  
Response Phenotype ◽  
Th1 And Th2

AbstractT 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 F1 hybrid (SWR×SJL) F1, 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.

Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): H-2 linked genes determine worm survival

Parasitology ◽  
1991 ◽  
Vol 103 (1) ◽  
pp. 157-164 ◽  
Author(s):  
J. M. Behnke ◽  
F. N. Wahid
Keyword(s):  
Primary Infection ◽  
Congenic Mouse ◽  
Mouse Strains ◽  
Gene Products ◽  
Heligmosomoides Polygyrus ◽  
Duration Of Infection ◽  
Response Phenotype ◽  
Nematospiroides Dubius ◽  
Resistance To Infection ◽  
Congenic Mouse Strains

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.

scholarly journals Immunological relationships during primary infection with Heligmosomoides polygyrus. Regulation of fast response phenotype by H-2 and non-H-2 genes

Parasitology ◽  
1993 ◽  
Vol 107 (3) ◽  
pp. 343-350 ◽  
Author(s):  
F. N. Wahid ◽  
J. M. Behnke
Keyword(s):  
Fast Response ◽  
Antibody Responses ◽  
Mouse Strains ◽  
Hybrid Progeny ◽  
Heligmosomoides Polygyrus ◽  
Response Phenotype ◽  
Mhc Haplotype ◽  
Slow Responder ◽  
Dominant Genes ◽  
Responder Mouse

SummaryThe inheritance of response phenotype to Heligmosomoides polygyrus was investigated in Fl hybrid progeny of fast and slow responder mouse strains. The fast responses of SJL(H-2s) and SWR(H-2q) mice were mediated by dominant genes complementing each other in Fl hybrids which lost worms earlier and produced faster parasite-specific IgG1 antibody responses than either parent. However, the response of Fl hybrids from crosses of C57BL/10 (B10, H-2b) mice with either SJL or SWR differed from that of the parental strains and from each other: (B10 × SWR)F1 lost worms earlier than SWR whilst (B10 × SJL)F1 lost worms later than SJL mice. The Fl progeny of SJL mice with congenic strains B10.G (H-2q) and B10.S (H-2s) lost worms as quickly as SJL. Therefore, the response phenotype mediated by the genome of SJL mice was unaffected by H-2 heterozygosity (with H-2q) or homozygosity (H-2s) despite heterozygosity with B10 background genes, but was slowed significantly by heterozygosity with H-2b. All hybrids involving heterozygosity with B10, irrespective of MHC haplotype or background, failed to clear worms completely, in each case a proportion of mice harbouring residual worm burdens after loss of worms from parental strains.

scholarly journals Importance of immunoglobulin E (IgE) in the protective mechanism against gastrointestinal nematode infection: looking at the intestinal mucosae

2001 ◽  
Vol 43 (5) ◽  
pp. 291-299 ◽  
Author(s):  
Deborah NEGRÃO-CORRÊA
Keyword(s):  
Immunoglobulin E ◽  
Trichinella Spiralis ◽  
Gastrointestinal Nematode ◽  
Nematode Species ◽  
Specific Ige ◽  
Gastrointestinal Nematodes ◽  
Experimental Models ◽  
Protective Mechanism ◽  
Heligmosomoides Polygyrus ◽  
Strongyloides Venezuelensis

This review discusses experimental evidences that indicate the IgE participation on the effector mechanisms that leads to gastrointestinal nematode elimination. Data discussed here showed that, for most experimental models, the immune response involved in nematode elimination is regulated by Th-2 type cytokines (especially IL-4). However, the mechanism(s) that result in worm elimination is not clear and might be distinct in different nematode species. Parasite specific IgE production, especially the IgE produced by the intestinal mucosae or associated lymphoid organs could participate in the intestinal elimination of Trichinella spiralis from infected rats. Intestinal IgE may also be important to the protective mechanism developed against other gastrointestinal nematodes that penetrate the murine duodenum mucosa tissue, such as Strongyloides venezuelensis and Heligmosomoides polygyrus. At least in Trichinella spiralis infected rats, the results indicated that intestinal IgE might work independently from mast cell degranulation for worm elimination.

Immunological realtionships during primary infection with Heligmosomides polygyrus (Nematospiroides dubius): expulsion of adult worms from fast responder syngeneic and hybrid strains of mice

Parasitology ◽  
1989 ◽  
Vol 98 (3) ◽  
pp. 459-469 ◽  
Author(s):  
F. N. Wahid ◽  
M. Robinson ◽  
J. M Behnke
Keyword(s):  
High Intensity ◽  
Primary Infection ◽  
Time Course ◽  
The Other ◽  
Mouse Strains ◽  
Heligmosomoides Polygyrus ◽  
Worm Expulsion ◽  
Nematospiroides Dubius ◽  
The One ◽  
Identical Gene

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.

The intensity and duration of primary Heligmosomoides polygyrus infection in TO mice modify acquired immunity to secondary challenge

2000 ◽  
Vol 74 (3) ◽  
pp. 225-231 ◽  
Author(s):  
B.B. Fakae ◽  
L.J.S. Harrison ◽  
M.M.H. Sewell
Keyword(s):  
Gastrointestinal Nematode ◽  
Intestinal Wall ◽  
Antibody Responses ◽  
Chronic Infections ◽  
Heligmosomoides Polygyrus ◽  
Larval Stages ◽  
Secondary Challenge ◽  
Larval Infection ◽  
Specific Antigens ◽  
Somatic Antigens

AbstractThe effect of dose and duration of immunizing infections of Heligmosomoides polygyrus on protection against homologous challenge was studied in female TO mice. Primary infections were terminated at various levels with pyrantel embonate (adult infections) or ivermectin (larval infections) and mice were then challenged with 500 infective larvae (L3). The level of protection to secondary challenge positively correlated with the intensity of the primary immunizing infection but truncation of larval infection produced significantly better protection than termination of the adult nematode infection. The duration of the primary larval infection (1–6 days) positively correlated with the level of protection to secondary challenge, antibody responses and the proportion of circulating eosinophils. Histological changes in the gastrointestinal tract, peripheral leucocytic changes and antibody responses of the mice to H. polygyrus adult somatic antigens indicate both a cellular and humoral basis of host immunity to secondary challenge. Although the TO mice are slow responders in that they harbour chronic infections, immunization by intramucosal killing of the larval stage produced strong protection against secondary challenge infection. The presence of dead immunogenic larval stages within the intestinal wall may well be an important factor, since it exposes the host to stage specific antigens at an appropriate location. The implications of the findings for the control of gastrointestinal nematode infections are also discussed.

scholarly journals Genetic Control of Mammalian Meiotic Recombination. I. Variation in Exchange Frequencies Among Males From Inbred Mouse Strains

Genetics ◽  
2002 ◽  
Vol 162 (1) ◽  
pp. 297-306 ◽  
Author(s):  
Kara E Koehler ◽  
Jonathan P Cherry ◽  
Audrey Lynn ◽  
Patricia A Hunt ◽  
Terry J Hassold
Keyword(s):  
Meiotic Recombination ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Male Meiosis ◽  
Mouse Strains ◽  
Recombination Rates ◽  
The Mean ◽  
Genetic Background Effects ◽  
Exchange Patterns ◽  
Positive Interference

AbstractGenetic background effects on the frequency of meiotic recombination have long been suspected in mice but never demonstrated in a systematic manner, especially in inbred strains. We used a recently described immunostaining technique to assess meiotic exchange patterns in male mice. We found that among four different inbred strains—CAST/Ei, A/J, C57BL/6, and SPRET/Ei—the mean number of meiotic exchanges per cell and, thus, the recombination rates in these genetic backgrounds were significantly different. These frequencies ranged from a low of 21.5 exchanges in CAST/Ei to a high of 24.9 in SPRET/Ei. We also found that, as expected, these crossover events were nonrandomly distributed and displayed positive interference. However, we found no evidence for significant differences in the patterns of crossover positioning between strains with different exchange frequencies. From our observations of >10,000 autosomal synaptonemal complexes, we conclude that achiasmate bivalents arise in the male mouse at a frequency of 0.1%. Thus, special mechanisms that segregate achiasmate chromosomes are unlikely to be an important component of mammalian male meiosis.

scholarly journals EVIDENCE THAT TWO LOCI PREDOMINANTLY DETERMINE THE DIFFERENCE IN SUSCEPTIBILITY TO THE HIGH PRESSURE NEUROLOGIC SYNDROME TYPE I SEIZURE IN MICE

Genetics ◽  
1981 ◽  
Vol 99 (2) ◽  
pp. 285-307
Author(s):  
R D McCall ◽  
D Frierson
Keyword(s):  
High Pressure ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Chromosome 17 ◽  
Seizure Threshold ◽  
Mouse Strains ◽  
Compression Rate ◽  
Type I ◽  
Major Locus ◽  
The Difference

ABSTRACT Most mammals tested, when exposed to increasing pressure in helium/oxygen atmospheres, exhibit progressive motor disturbances culminating in two, usually successive, well-differentiated convulsive seizures. The seizures are highly reproducible components of the constellation of events that collectively constitute the High Pressure Neurologic Syndrome (HPNS). In the present study, we present evidence that the mean difference in seizure threshold pressures of the first seizure to occur (HPNS Type I) between inbred mouse strains DBA/2J and C57BL/6J is predominantly determined (> 60%) by the expression of a major locus—possibly linked to the H-2 locus on chromosome 17—and a minor locus, probably unlinked. This outcome is derived from applications of the maximum likelihood modeling procedure of Elston and Stewart (1973) and Stewart and Elston (1973) to eleven models of genetic determinacy and tests (including breeding tests) of "preferred" models so derived using BXD recombinant inbred strains that show the following: The major locus exhibits conditional dominance characteristics depending upon compression rate and minor locus genotype. At a constant mean compression rate of 100 atm hr-1, the major locus manifests strong, though incomplete, dominance apparently independent of minor locus genotype. Its expression is, however, highly sensitive to compression rate, losing its dominance altogether at a linear rate of 1,000 atm hr-1. The major locus interacts with the weakly dominant and relatively compression-rate-insensitive minor locus to retain dominance at fast compression only when the dominant alleles of both loci are present. A principal finding of this study is that employing two compression rates permits fuller genetic characterization of murine high-pressure seizure susceptibility differences than could be achieved by use of a single compression rate.

scholarly journals Discovery and refinement of muscle weight QTLs in B6 × D2 advanced intercross mice

2014 ◽  
Vol 46 (16) ◽  
pp. 571-582 ◽  
Author(s):  
P. Carbonetto ◽  
R. Cheng ◽  
J. P. Gyekis ◽  
C. C. Parker ◽  
D. A. Blizard ◽  
...  
Keyword(s):  
Inbred Strains ◽  
Mouse Strains ◽  
Missense Mutations ◽  
Muscle Weight ◽  
Hindlimb Muscles ◽  
Hindlimb Muscle ◽  
Causal Genes ◽  
Snp Panel ◽  
Genomic Regions ◽  
Genetic Contributions

The genes underlying variation in skeletal muscle mass are poorly understood. Although many quantitative trait loci (QTLs) have been mapped in crosses of mouse strains, the limited resolution inherent in these conventional studies has made it difficult to reliably pinpoint the causal genetic variants. The accumulated recombination events in an advanced intercross line (AIL), in which mice from two inbred strains are mated at random for several generations, can improve mapping resolution. We demonstrate these advancements in mapping QTLs for hindlimb muscle weights in an AIL ( n = 832) of the C57BL/6J (B6) and DBA/2J (D2) strains, generations F8–F13. We mapped muscle weight QTLs using the high-density MegaMUGA SNP panel. The QTLs highlight the shared genetic architecture of four hindlimb muscles and suggest that the genetic contributions to muscle variation are substantially different in males and females, at least in the B6D2 lineage. Out of the 15 muscle weight QTLs identified in the AIL, nine overlapped the genomic regions discovered in an earlier B6D2 F2 intercross. Mapping resolution, however, was substantially improved in our study to a median QTL interval of 12.5 Mb. Subsequent sequence analysis of the QTL regions revealed 20 genes with nonsense or potentially damaging missense mutations. Further refinement of the muscle weight QTLs using additional functional information, such as gene expression differences between alleles, will be important for discerning the causal genes.

scholarly journals SERPINB10 contributes to asthma by inhibiting the apoptosis of allergenic Th2 cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yuqing Mo ◽  
Ling Ye ◽  
Hui Cai ◽  
Guiping Zhu ◽  
Jian Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Allergic Asthma ◽  
Cd4 T Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Allergic Inflammation ◽  
Specific Ige ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Th2 Response ◽  
Th1 And Th2

Abstract Background Serine peptidase inhibitor, clade B, member 10 (SERPINB10) contributes to allergic inflammation in asthma. However, its role in the T-helper type 2 (Th2) response of allergic asthma is not known. The goal of this study was to unveil the function of SERPINB10 in the Th2 response of allergic asthma and the mechanism by which SERPINB10 affects the viability of Th2 cells. Methods Th2 cytokines and serum levels of house dust mite (HDM)-specific IgE in bronchoalveolar lavage fluid were examined by ELISA in an HDM-induced asthma model. The number and apoptosis of Th1 and Th2 cells in mouse lungs were measured by flow cytometry. Naïve CD4 T cells from patients with asthma were cultured under appropriate polarizing conditions to generate Th1 and Th2 cells. SERPINB10 expression in polarized Th1 and Th2 cells was quantified by real-time reverse transcription-quantitative polymerase chain reaction. SERPINB10 expression was knocked down in human CD4 T cells with lentivirus. Results Knockdown of SERPINB10 expression significantly diminished HDM-induced Th2 cytokine secretion and level of HDM-specific IgE. After HDM exposure, SERPINB10-knockdown mice had diminished numbers of Th2 cells, but similar numbers of Th1 cells, compared with those in negative-control mice. Th2 cells of SERPINB10-knockdown mice were more susceptible to apoptosis than that of control mice. Stimulating T-cell receptors (TCRs) with anti-CD3 antibody caused upregulation of SERPINB10 expression in polarized Th2 cells, but not polarized Th1 cells. Knockdown of SERPINB10 expression resulted in fewer numbers and greater apoptosis of polarized Th2 cells. Conclusion Our results suggest that SERPINB10 may contribute to allergic inflammation and the Th2 response of asthma by inhibiting the apoptosis of Th2 cells.

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