Influence of genes within the MHC on mortality and brain cyst development in mice infected with Toxoplasma gondii: kinetics of immune regulation in BALB H-2 congenic mice

J M Blackwell, C W Roberts, J Alexander, Craig Roberts

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Previous work has shown that genes within the major histocompatibility complex (MHC) of the mouse influence resistance and susceptibility to Toxoplasma gondii infection. Initial studies presented here using B10 H-2 congenic and recombinant haplotype mice inoculated via the oral route with the low virulence Beverley strain of T. gondii confirm the D region localization of MHC-linked control of brain cyst number. All B10 mice were, however, exquisitely sensitive to minor changes in virulence of the parasite inoculum resulting in high mortality during the early acute phase of infection. Further experiments examining mortality and brain cyst number in BALB MHC congenic mice inoculated via different routes indicated that the BALB background would provide a more favourable genetic environment in which to analyse kinetics of MHC controlled immune regulation following infection via the natural (oral) route. In studies comparing d and k haplotype mice a dramatic inverse relationship between splenic CD4:CD8 T cell ratios and brain cyst number was observed, particularly in the strain (BALB/K; H-2k) most susceptible to high brain cyst numbers and subsequent toxoplasmic encephalitis. Of particular interest was the observation that splenomegaly and the relative increase in the splenic CD8 T cell population preceded and accompanied the very dramatic and rapid increase in brain cyst formation. The results suggest that the too rapid development of a potent anti-parasite response in the viscera may drive the parasite to encyst in the brain.
LanguageEnglish
Pages317-324
Number of pages8
JournalParasite Immunology
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 1993

Fingerprint

Congenic Mice
Toxoplasma
Major Histocompatibility Complex
Cysts
Mortality
Brain
Genes
Parasites
Haplotypes
Virulence
T-Lymphocytes
Viscera
Toxoplasmosis
Splenomegaly
Encephalitis
Infection
Population

Keywords

  • animals
  • antibodies, protozoan
  • antigens, CD4
  • antigens, CD8
  • disease models, animal
  • enzyme-linked immunosorbent assay
  • female
  • flow cytometry
  • genes, MHC class I
  • H-2 antigens
  • haplotypes
  • major histocompatibility Complex
  • mice
  • mice, inbred BALB C
  • mice, inbred C57BL
  • t-lymphocytes
  • time factors
  • toxoplasmosis, animal
  • toxoplasmosis, cerebral

Cite this

@article{5ddd0f49d1cd4b82a8c77e1c6d9577d5,
title = "Influence of genes within the MHC on mortality and brain cyst development in mice infected with Toxoplasma gondii: kinetics of immune regulation in BALB H-2 congenic mice",
abstract = "Previous work has shown that genes within the major histocompatibility complex (MHC) of the mouse influence resistance and susceptibility to Toxoplasma gondii infection. Initial studies presented here using B10 H-2 congenic and recombinant haplotype mice inoculated via the oral route with the low virulence Beverley strain of T. gondii confirm the D region localization of MHC-linked control of brain cyst number. All B10 mice were, however, exquisitely sensitive to minor changes in virulence of the parasite inoculum resulting in high mortality during the early acute phase of infection. Further experiments examining mortality and brain cyst number in BALB MHC congenic mice inoculated via different routes indicated that the BALB background would provide a more favourable genetic environment in which to analyse kinetics of MHC controlled immune regulation following infection via the natural (oral) route. In studies comparing d and k haplotype mice a dramatic inverse relationship between splenic CD4:CD8 T cell ratios and brain cyst number was observed, particularly in the strain (BALB/K; H-2k) most susceptible to high brain cyst numbers and subsequent toxoplasmic encephalitis. Of particular interest was the observation that splenomegaly and the relative increase in the splenic CD8 T cell population preceded and accompanied the very dramatic and rapid increase in brain cyst formation. The results suggest that the too rapid development of a potent anti-parasite response in the viscera may drive the parasite to encyst in the brain.",
keywords = "animals, antibodies, protozoan, antigens, CD4, antigens, CD8, disease models, animal, enzyme-linked immunosorbent assay, female, flow cytometry, genes, MHC class I, H-2 antigens, haplotypes, major histocompatibility Complex, mice, mice, inbred BALB C, mice, inbred C57BL, t-lymphocytes, time factors, toxoplasmosis, animal, toxoplasmosis, cerebral",
author = "Blackwell, {J M} and Roberts, {C W} and J Alexander and Craig Roberts",
year = "1993",
month = "6",
doi = "10.1111/j.1365-3024.1993.tb00616.x",
language = "English",
volume = "15",
pages = "317--324",
journal = "Parasite Immunology",
issn = "0141-9838",
number = "6",

}

Influence of genes within the MHC on mortality and brain cyst development in mice infected with Toxoplasma gondii : kinetics of immune regulation in BALB H-2 congenic mice. / Blackwell, J M; Roberts, C W; Alexander, J; Roberts, Craig.

In: Parasite Immunology, Vol. 15, No. 6, 06.1993, p. 317-324.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Influence of genes within the MHC on mortality and brain cyst development in mice infected with Toxoplasma gondii

T2 - Parasite Immunology

AU - Blackwell, J M

AU - Roberts, C W

AU - Alexander, J

AU - Roberts, Craig

PY - 1993/6

Y1 - 1993/6

N2 - Previous work has shown that genes within the major histocompatibility complex (MHC) of the mouse influence resistance and susceptibility to Toxoplasma gondii infection. Initial studies presented here using B10 H-2 congenic and recombinant haplotype mice inoculated via the oral route with the low virulence Beverley strain of T. gondii confirm the D region localization of MHC-linked control of brain cyst number. All B10 mice were, however, exquisitely sensitive to minor changes in virulence of the parasite inoculum resulting in high mortality during the early acute phase of infection. Further experiments examining mortality and brain cyst number in BALB MHC congenic mice inoculated via different routes indicated that the BALB background would provide a more favourable genetic environment in which to analyse kinetics of MHC controlled immune regulation following infection via the natural (oral) route. In studies comparing d and k haplotype mice a dramatic inverse relationship between splenic CD4:CD8 T cell ratios and brain cyst number was observed, particularly in the strain (BALB/K; H-2k) most susceptible to high brain cyst numbers and subsequent toxoplasmic encephalitis. Of particular interest was the observation that splenomegaly and the relative increase in the splenic CD8 T cell population preceded and accompanied the very dramatic and rapid increase in brain cyst formation. The results suggest that the too rapid development of a potent anti-parasite response in the viscera may drive the parasite to encyst in the brain.

AB - Previous work has shown that genes within the major histocompatibility complex (MHC) of the mouse influence resistance and susceptibility to Toxoplasma gondii infection. Initial studies presented here using B10 H-2 congenic and recombinant haplotype mice inoculated via the oral route with the low virulence Beverley strain of T. gondii confirm the D region localization of MHC-linked control of brain cyst number. All B10 mice were, however, exquisitely sensitive to minor changes in virulence of the parasite inoculum resulting in high mortality during the early acute phase of infection. Further experiments examining mortality and brain cyst number in BALB MHC congenic mice inoculated via different routes indicated that the BALB background would provide a more favourable genetic environment in which to analyse kinetics of MHC controlled immune regulation following infection via the natural (oral) route. In studies comparing d and k haplotype mice a dramatic inverse relationship between splenic CD4:CD8 T cell ratios and brain cyst number was observed, particularly in the strain (BALB/K; H-2k) most susceptible to high brain cyst numbers and subsequent toxoplasmic encephalitis. Of particular interest was the observation that splenomegaly and the relative increase in the splenic CD8 T cell population preceded and accompanied the very dramatic and rapid increase in brain cyst formation. The results suggest that the too rapid development of a potent anti-parasite response in the viscera may drive the parasite to encyst in the brain.

KW - animals

KW - antibodies, protozoan

KW - antigens, CD4

KW - antigens, CD8

KW - disease models, animal

KW - enzyme-linked immunosorbent assay

KW - female

KW - flow cytometry

KW - genes, MHC class I

KW - H-2 antigens

KW - haplotypes

KW - major histocompatibility Complex

KW - mice

KW - mice, inbred BALB C

KW - mice, inbred C57BL

KW - t-lymphocytes

KW - time factors

KW - toxoplasmosis, animal

KW - toxoplasmosis, cerebral

U2 - 10.1111/j.1365-3024.1993.tb00616.x

DO - 10.1111/j.1365-3024.1993.tb00616.x

M3 - Article

VL - 15

SP - 317

EP - 324

JO - Parasite Immunology

JF - Parasite Immunology

SN - 0141-9838

IS - 6

ER -