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Genetic control of streptococcus-induced hepatic granulomatous lesions in mice
C Y Chen1, S A Cohen, M B Zaleski
1Department of Microbiology, State University of New York, Buffalo 14214.
Abstract:
Hepatic granulomatous lesions were induced in mice by a single intraperitoneal injection of 3 mg of disrupted Streptococcus pyogenes cell-wall material. Mice carrying the H-2b or H-2k haplotypes were highly susceptible to the induction and three weeks after the injection produced numerous granulomas. In contrast, mice of the H-2d haplotype were resistant and produced only a few hepatic granulomas. Resistance was inherited as a dominant trait and in the backcross generation segregated together with the H-2d phenotype. Testing of the H-2-recombinant mice indicated that the putative gene(s) determining resistance/susceptibility is located to the right of the S and to the left of the D region. This location corresponds to the recently described gene cluster consisting of tumor necrosis factor (TNF) and lymphotoxin genes and several BAT sequences. The known effect of TNF on granuloma formation in mice is consistent with a possible effect of TNF genes, and their variants, on S. pyogenes-inducibility of hepatic granulomas in mice.
Insights
Mice with specific H-2 haplotypes show varying susceptibility to Streptococcus pyogenes-induced liver granulomas. Genetic mapping suggests a resistance gene near tumor necrosis factor (TNF) genes.
Area of Science:
- Immunology
- Genetics
- Microbiology
Background:
- Streptococcus pyogenes infections can lead to granulomatous inflammation.
- Murine models are crucial for studying host-pathogen interactions and genetic influences on disease susceptibility.
Purpose of the Study:
- To investigate the genetic basis of susceptibility and resistance to Streptococcus pyogenes-induced hepatic granulomas in mice.
- To identify the chromosomal location of genes controlling this immune response.
Main Methods:
- Induction of hepatic granulomas in mice using Streptococcus pyogenes cell-wall material.
- Phenotypic analysis of granuloma formation across different H-2 haplotypes (H-2b, H-2k, H-2d).
- Genetic analysis using backcross and H-2-recombinant mouse strains to map the responsible gene(s).
Main Results:
- Mice with H-2b and H-2k haplotypes were highly susceptible, developing numerous granulomas.
- Mice with the H-2d haplotype exhibited resistance, forming significantly fewer granulomas.
- Resistance was inherited as a dominant trait and mapped to a region between the S and D regions of the H-2 complex, overlapping with TNF and lymphotoxin genes.
Conclusions:
- The H-2 haplotype significantly influences the susceptibility to Streptococcus pyogenes-induced hepatic granulomas.
- The genetic locus controlling this response is located near the tumor necrosis factor (TNF) gene cluster, suggesting a role for TNF in regulating granuloma formation.