Development of Pulmonary Chlamydia Infection in Inbred Mice Strains Differentiated by Genetically Determined Sensitivity to Tuberculosis Infection

Mice of I/St strain develop severe lung inflammation and die shortly following infection with virulent mycobacteria. Susceptibility does not depend upon the Nramp1 gene, as I/St mice carry its resistant allele, but is controlled by a few interacting QTL mapped to chromosomes 3, 9 and 17. To find out whether tuberculosis-susceptible I/St mice are susceptible to other intracellular bacteria, we investigated taxonomically distant pathogen, Chlamydia pneumoniae. Comparison of I/St and TB-resistant A/Sn mice (both Nramp1(r)) demonstrated that the former are more susceptible to chlamydia, displaying a significantly shortened survival time following challenge (I/St 9.2 +/- 1.2 days, A/Sn - 22.0 +/- 2.0 days (p < 0.001). To estimate the degree of chlamydial multiplication in the lungs, we established a quantitative real-time polymerase chain reaction (PCR)- based method which allows enumeration of the parasite's genome equivalents in infected tissue from 1 to 16 days after challenge. Interstrain difference of chlamydia burden in lungs we obtained after 24 hours after infection only. Multiplication of chlamydia in the lungs was controlled efficiently after day 4 of infection, and the numbers of genome equivalents dropped slightly by day 8 both in I/St and A/Sn mice. Lung pathology develops more rapidly in I/St compared to A/Sn mice following infection with chlamydia, despite their similar ability to control bacterial multiplication. Lung tissue of susceptible I/St mice was markedly infiltrated with macrophages (p < 0.01), which differed significantly from the lungs of resistant A/Sn mice. In agreement with higher macrophage content in the lungs, significantly more macrophage-derived proinflammatory cytokines TNF-alpha and IL-6 were detected in lung tissue homogenates obtained from I/St mice (p < 0.05). Because the prominent differences in survival time did not correlate with permanent differences in bacterial multiplication, we suggest that both infections trigger fatal pathological processes whose dynamics depend strongly upon the host genetics.