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

Parasite Immunology - Tập 15 Số 6 - Trang 317-324 - 1993
Jenefer M. Blackwell1, Craig W. Roberts2, James Alexander2
1Department of Medicine, University of Cambridge Clinical School, Level 5, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK. .
2Department of Immunology, University of Strathclyde, The Todd Centre, 31 Taylor Street, Glasgow, G4 0NR, UK

Tóm tắt

SummaryPrevious 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.

Từ khóa


Tài liệu tham khảo

Black C. M., 1989, Effect of recombinant tumour necrosis factor on acute infection in mice with Toxoplasma gondii or Trypanosoma cruzi, Immunology, 68, 570

10.1016/0003-2697(76)90527-3

Brown C. R., 1990, Class I MHC genes and CD8+ T cells determine cyst number in Toxoplasma gondii infection, Journal of Immunology, 145, 3438, 10.4049/jimmunol.145.10.3438

Chang H. R., 1990, Role of TNF and IL‐1 in infections with Toxoplasma gondii, Immunology, 69, 33

Chang H. R., 1992, Role of tumour necrosis factor in chronic murine Toxoplasma gondii encephalitis, Immunology and Infectious Diseases, 2, 61

10.1084/jem.175.3.683

10.7883/yoken1952.36.343

Gazzinelli R. T., 1991, Synergistic role of CD4+ and CD8+ T lymphocytes in IFN‐γ production and protective immunity induced by an attenuated Toxoplasma gondii vaccine, Journal of Immunology, 146, 286, 10.4049/jimmunol.146.1.286

10.1111/j.1365-3024.1992.tb00015.x

HunterC. A. RobertsC. W.&AlexanderJ.(1992b)Kinetics of cytokine mRNA production in the brains of mice with progressive toxoplasmic encephalitis. European Journal of Immunology (in press).

10.1007/BF00927816

Johnson L. L., 1992, A protective role for endogenous tumour necrosis factor in Toxoplasma gondii infection, Infection and Immunity, 60, 1979, 10.1128/iai.60.5.1979-1983.1992

10.1093/infdis/151.4.739

McLeod R., 1989, Genetic regulation of early survival and cyst number after peroral Toxoplasma gondii infection of AXB/BXA recombinant inbred and B10 congenic mice, Journal of Immunology, 143, 3031, 10.4049/jimmunol.143.9.3031

10.1111/j.1365-2249.1991.tb08150.x

10.1001/jama.1941.02820090001001

Sibley L. D., 1991, TNF‐α triggers anti‐toxoplasmal activity in IFN‐γ primed macrophages, Journal of Immunology, 147, 2340, 10.4049/jimmunol.147.7.2340

10.1126/science.3107127

Suzuki Y., 1988, Dual regulation of resistance against Toxoplasma gondii infection by Lyt‐2+ and Lyt‐1+, L3T4+ T cells in mice, Journal of Immunology, 140, 3943, 10.4049/jimmunol.140.11.3943

Suzuki Y., 1989, Importance of endogenous IFN‐γ for prevention of toxoplasmic encephalitis in mice, Journal of Immunology, 143, 2045, 10.4049/jimmunol.143.6.2045

Suzuki Y., 1990, Treatment of toxoplasmic encephalitis in mice with recombinant gamma interferon, Infection and Immunity, 58, 3050, 10.1128/iai.58.9.3050-3055.1990

Suzuki Y., 1991, Gene(s) within the H‐2D region determines the development of toxoplasmic encephalitis in mice, Immunology, 74, 732

10.1136/jcp.29.2.150

Williams D. M., 1978, Genetic control of murine resistance to Toxoplasma gondii, Infection and Immunity, 19, 416, 10.1128/iai.19.2.416-420.1978

Thông tin
Thông tin xuất bản

Parasite Immunology

Tập 15 Số 6

317-324

Thông tin tác giả