Consequence of Nramp1 deletion to Mycobacterium tuberculosis infection in mice

Abstract

129sv mice functionally deleted of the antimicrobial resistance gene, Nramp1, were found to be as resistant as wild-type mice to infection with the virulent H37Rv strain of Mycobacterium tuberculosis, as determined by monitoring bacterial growth in major organs and recording host survival times. Death of infected mice of both types was associated with extensive infection-induced pathology in the lungs but not in other major organs. These findings are in keeping with the view that Nramp1 is of limited importance in resistance to tuberculosis in mice.

FIG. 1

Growth of M. tuberculosis H37Rv in lungs, livers, spleens, and kidneys of Nramp1^−/− and wild-type (Nramp1^+/+) mice inoculated i.v. with 10⁴ CFU of bacilli. There was no significant difference in the ability of mutant and wild-type mice to control bacterial replication over 130 days of infection except for day 130 in the spleen, where the differences between the means was significant (P < 0.05). Means ± standard errors of five mice per group per time point are shown.

FIG. 2

Survival times of 10 Nramp1^−/− and 10 wild-type mice inoculated i.v. with 10⁴ CFU of H37Rv. There was no significant difference (P > 0.2) between the survival times of mutant and wild-type mice.

FIG. 3

Macroscopic appearance of major organs of wild-type (left) and Nramp1^−/− (right) mice harvested on day 200 of infection initiated with 10⁴ CFU of H37Rv i.v. Shown from top to bottom are the lungs, liver, spleen, and left kidney. Only the lungs of both types of mice show disease.

FIG. 4

Survival times of 10 Nramp1^−/− and 10 wild-type mice infected via the respiratory route with 2 × 10² CFU of H37Rv. There was no significant difference (P > 0.6) between the survival times.

FIG. 5

Number of H37Rv CFU in livers and spleens of Nramp1^−/− and Nramp1^+/+ mice given 10³ CFU of H37Rv i.v. 30 days earlier. No bacteria were detected in the lungs. Means ± standard errors of five mice per group are shown.