MHCII, Tlr4 and Nramp1 genes control host pulmonary

each independently important in pulmonary immu-nity. To determine the effect of these genes on host resistance, mice carrying various combinations of functional alleles for these three genes were experi-mentally challenged with the opportunistic bacte-rium, Pasteurella pneumotropica. MHCII-/-, Tlr4d/d, and Nramp1s/s mice were significantly more suscep-tible to experimental infections by P. pneumotropica after intranasal challenge compared to mice carrying functional alleles at only one of those genes. P. pneu-motropica 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 MHCII1/1, Tlr4d/d mice. It is interesting that the Nramp1 gene contri-bution 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. J. Leu-koc. Biol. 69: 381–386; 2001. Key Words: genotypes z lungs z mic