MHCII, Tlr4 and Nramp1 genes control host pulmonary resistance against the opportunistic bacterium Pasteurella pneumotropica.
MHCII, Tlr4, and Nramp1 genes are each independently important in pulmonary immunity. To determine the effect of these genes on host resistance, mice carrying various combinations of functional alleles for these three genes were experimentally challenged with the opportunistic bacterium, Pasteurella pneumotropica. MHCII-/-, Tlr4d/d, and Nramp1s/s mice were significantly more susceptible to experimental infections by P. pneumotropica after intranasal challenge compared to mice carrying functional alleles at only one of those genes. P. pneumotropica were cultured from the lungs of challenged mice, and the severity of the pneumonia strongly correlated with the number of isolated bacteria. Mice with the genotype MHCII-/- Tlr4n/n genotype were less susceptible to pneumonia than MHCII+/+, Tlr4d/d mice. It is interesting that the Nramp1 gene contribution to host resistance was apparent only in the absence of functional MHCII or Tlr4 genes. These data suggest that MHCII, Tlr4, and Nramp1 genes are important to pulmonary bacterial resistance.
Division of Biology, Kansas State University, Manhattan 66506-4901, USA. skcbiol@ksu.edu
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D000483:Alleles; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology; D027682:Cation Transport Proteins; D003433:Crosses, Genetic; D029721:Drosophila Proteins; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010325:Pasteurella; D010326:Pasteurella Infections / Q000235:genetics* / Q000276:immunology*; D018410:Pneumonia, Bacterial / Q000235:genetics* / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099173:Natural Resistance-associated Macrophage Protein 1
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D000099173:Natural Resistance-associated Macrophage Protein 1