Enhanced mortality despite control of lung infection in mice aerogenically infected with a Mycobacterium tuberculosis mce1 operon mutant.
Mycobacterium tuberculosis causes a variety of host clinical outcomes. We previously showed that M. tuberculosis disrupted in an operon called mce1 proliferates unchecked in BALB/c mouse lungs. The observed outcome could be attributed either to the mutant bacterial burden or to the host immunopathologic response. To differentiate these possibilities, we studied the outcomes of infection in a mouse strain (C57BL/6) less susceptible to M. tuberculosis than BALB/c. We found that the mutant infection reached a plateau in the lungs at a rate similar to that of the wild type. All mice infected with the mutant, but only half of the groups of mice infected with the wild type or complemented strain, died by 40 weeks (p<0.05). At 12-21 weeks of infection, histological examination of the lungs of mice infected with the mutant showed a diffuse pattern of lymphocyte infiltration, while that of mice infected with the other strains exhibited a nodular cellular infiltration pattern. Surprisingly, the number of bacilli recovered from the lungs was similar in all three groups. These observations suggest that rather than the bacterial burden, products of the mce1 operon may directly or indirectly modulate the host immune response that is protective to both the tubercle bacilli and the host.
Lima
Patricia
P
Division of Infectious Diseases, School of Public Health, 140 Warren Hall, University of California, Berkeley, CA 94720, USA.
Sidders
Ben
B
Morici
Lisa
L
Reader
Rachel
R
Senaratne
Ryan
R
Casali
Nicola
N
Riley
Lee W
LW
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D015169:Colony Count, Microbial; D005260:Female; D017353:Gene Deletion; D005816:Genetic Complementation Test; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity*; D009876:Operon / Q000235:genetics; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D014376:Tuberculosis / Q000382:microbiology* / Q000401:mortality*
D001426:Bacterial Proteins; C473802:mammalian cell entry protein Mce1A, Mycobacterium tuberculosis