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Mouse genetic locus Lps influences susceptibility to Neisseria meningitidis infection
J P Woods1, J A Frelinger, G Warrack
1Department of Microbiology and Immunology, University of North Carolina, School of Medicine, Chapel Hill 27599.
Abstract:
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 (Lpsd) mice and each of the other strains (all Lpsn). We confirmed the association of the Lpsd genotype with susceptibility by using coisogenic strains from two widely separated mouse lineages: C3H and B10. Lpsd mice experienced a 1,000-fold proliferation of bacteria and were bacteremic for days before clearing the infection. In contrast, Lpsn 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 (Lpsn) mice, suggesting that the Lps-related difference in susceptibility may involve a cellular response.
Insights
Mouse inbred strains show varying susceptibility to meningococcemia, a bacterial infection. The Lps locus significantly influences this susceptibility, with Lpsd mice exhibiting prolonged bacteremia compared to Lpsn mice.
Area of Science:
- Immunology
- Genetics
- Microbiology
Background:
- Meningococcemia, caused by Neisseria meningitidis, is a serious human disease.
- Understanding host genetic factors influencing susceptibility is crucial for disease control.
- Previous studies have identified various host loci affecting bacterial infections.
Purpose of the Study:
- To investigate the genetic basis of susceptibility to meningococcemia in inbred mouse strains.
- To identify specific host genetic loci that influence the course of meningococcemia.
Main Methods:
- Intraperitoneal injection of a serogroup C, serotype 2a Neisseria meningitidis isolate into multiple inbred mouse strains.
- Quantification of bacteremia levels and duration across different mouse strains.
- Genotyping for known host susceptibility loci including MHC, Ig, Ity, Hc, xid, Trf, and Lps.
Main Results:
- All tested mouse strains became bacteremic, but significant differences in bacteremia levels were observed, indicating host genome influence.
- No correlation was found between bacteremia levels and MHC, Ig, Ity, Hc, xid, or Trf loci.
- The Lps locus significantly influenced susceptibility, with C3H/HeJ (Lpsd) mice exhibiting higher and prolonged bacteremia compared to other strains (Lpsn).
- Coisogenic strains confirmed the association of the Lpsd genotype with increased bacterial proliferation and delayed clearance.
- In vitro studies showed no difference in bacterial growth in serum from Lpsd and Lpsn mice, suggesting a cellular basis for Lps-mediated susceptibility.
Conclusions:
- The Lps locus is a key determinant of susceptibility to meningococcemia in mice.
- Lpsd genotype is associated with a severe form of meningococcemia characterized by prolonged bacteremia and bacterial proliferation.
- The mechanism of Lps-mediated susceptibility likely involves host cellular responses rather than serum factors.