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. 2000 Sep;68(9):5462-5.
doi: 10.1128/IAI.68.9.5462-5465.2000.

Role of inducible nitric oxide synthase in resistance to Mycobacterium leprae in mice

L B Adams  1 , C K Job, J L Krahenbuhl
Affiliations

Role of inducible nitric oxide synthase in resistance to Mycobacterium leprae in mice

L B Adams et al. Infect Immun. 2000 Sep.

Abstract

The manifestation of leprosy in humans is largely determined by host immunity to Mycobacterium leprae and is a model for immunoregulation in a human disease. However, animal models available for exploration of the leprosy spectrum are inadequate. This study explored M. leprae infection in mice deficient in inducible nitric oxide synthase, and this report describes elements resembling borderline tuberculoid leprosy in humans.

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Figures

FIG. 1
FIG. 1
Effects of activated peritoneal MΦ from B6 and iNOS KO mice on M. leprae. (A) Viability of M. leprae recovered from control (open bars) or IFN-plus-lipopolysaccharide-activated (hatched bars) B6 MΦ incubated in the presence or absence of 500 μM AG or 500 μM L-NMA and from iNOS KO MΦ. Viability of bacilli was determined 48 h postinfection by radiorespirometric measurement of the oxidation of [14C]palmitic acid (19). (B) Nitrite levels in the culture supernatants were determined using the Griess reagent. Control versus activated MΦ: ∗∗, P < 0.01; ∗∗∗, P < 0.001.
FIG. 2
FIG. 2
Growth of M. leprae in mouse in footpads. B6 (circles) and iNOS KO (triangles) mice were infected in both hind footpads with 104 viable, nu/nu mouse-derived M. leprae organisms. At the indicated times postinfection, the number of AFB per footpad was determined. Open and closed symbols represent two independent experiments. Each symbol represents one mouse, except at the 4- and 6-month time points, where each symbol represents a pool of two mice. The threshold of counting ability (dotted line) is 3 × 103 AFB per footpad.
FIG. 3
FIG. 3
Granulomatous response in mouse footpads in response to infection with 104 M. leprae organisms. (A) Small granuloma around a neurovascular bundle in a B6 mouse at 15 months postinfection. It is composed primarily of spindle-shaped MΦ and a few lymphocytes (hematoxylin-and-eosin staining; bar, 100 μm). (B) The granuloma in an iNOS KO mouse at 15 months postinfection was over 10 times the size of that seen in B6 mice and was composed of epithelioid cells and numerous lymphocytes (hematoxylin-and-eosin staining; bar, 100 μm). (C) Higher-power view of the granuloma in iNOS KO mice to show the epithelioid cells with abundant cytoplasm bordered by a dense collection of lymphocytes (hematoxylin-and-eosin staining; bar, 50 μm). (D) The granuloma in iNOS KO mice infiltrated the striated muscles and partly destroyed them (hematoxylin-and-eosin staining; bar, 50 μm).
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References

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