MHCII, Tlr4 and Nramp1 genes control host pulmonary resistance against theopportunistic 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 w ere experimentally challenged with the opportunistic bacterium, Pasteurella pneumotropica. MHCII-/-, Tlr4(d/d), and Nramp1(s/s) mice were significantl y more susceptible to experimental infections by P. pneumotropica after int ranasal 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 numbe r of isolated bacteria. Mice with the genotype MHCII(-/-)Tlr4(n/n) genotype were less susceptible to pneuomonia than MHCII+/+, Tlr4(d/d) mice. It is i nteresting that the Namp1 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 res istance.