International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 205 - IMPACT OF THE MAJOR HISTOCOMPATIBILITY COMPLEX HAPLOTYPE IN RESISTANCE OF CONGENIC BALB MICE TO GROUP A STREPTOCOCCAL INFECTION

Goldmann O
GBF – German Research Centre for Biotechnology

Co-Authors: Müller A, Lengeling A, Chhatwal G S, Medina E
Institutions: GBF – German Research Centre for Biotechnology

Epidemiological studies revealed that susceptibility to group A streptococcal (GAS) infection can be influenced by host genetic factors. Human major histocompatibility complex (MHC) genes are genetic determinants of susceptibility to many immunopathological conditions. Interestingly, mouse strains highly susceptible to GAS infection shared the same H-2 haplotype (H-2k), while resistant strains display different H-2 haplotypes. Based on this observation and the availability of congenic mice from the BALB background carrying the MHC region of susceptible mice (BALB/k mice), we decided to determine the contribution of MHC genes to disease susceptibility to GAS infection. For this purpose, a comparative study was performed with congenic BALB mice of H-2k (BALB/k) and H-2d (BALB/c) haplotypes, which were systemically infected with S. pyogenes. The more severe outcome of infection in BALB/k was associated with high levels of inflammatory cytokines such as IFN-γ and IL-12. Since GAS produce several superantigens (GAS-Sags) which seem to be involved in the development of severe infections, the potential contribution of GAS-SAgs was investigated. T cells from BALB/k mice responded with higher proliferative activity to in vitro stimulation with GAS-SAgs and produced higher levels of INF-γ than those from BALB/c mice. Our results suggest that although a particular MHC haplotype might contribute to severity of infection, susceptibility to S. pyogenes seems to be primarily defined by other immune system-related genes of the MHC region. To narrow the region for further investigation of the responsible genes, backcrosses were performed between the F1 progeny (BALB/c x BALB/k) with the resistent parental BALB/c strain.


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