Mouse genetic locus Lps influences susceptibility to Neisseria meningitidis infection

We surveyed a number of inbred mouse strains for susceptibility to meningococcemia. Mice of all strains became bacteremic after intraperitoneal injection of a serogroup C, serotype 2a human disease isolate, but the strains differed in levels of bacteremia, indicating influences of the host genome on susceptibility. There was no significant correlation between level of bacteremia and differences at major histocompatibility or immunoglobulin loci; the Salmonella susceptibility locus, Ity; the complement C5 locus, Hc; the antibody response locus, xid; or the transferrin locus, Trf. However, the Lps locus, which influences a range of host cellular responses to endotoxin and affects susceptibility to Salmonella typhimurium, did influence susceptibility to meningococcemia. There were significant differences in levels of bacteremia between C3H/HeJ (Lps(d)) mice and each of the other strains (all Lps(n)). We confirmed the association of the Lps(d) genotype with susceptibility by using coisogenic strains from two widely separated mouse lineages: C3H and B10. Lps(d) mice experienced a 1,000-fold proliferation of bacteria and were bacteremic for days before clearing the infection. In contrast, Lps(n) mice cleared the bacteremia in less than 1 day. There was no difference in meningococcal growth in vitro in serum from C3H/HeJ and coisogenic C3H/HeN (Lps(n)) mice, suggesting that the Lps-related difference in susceptibility may involve a cellular response.