Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 33, Issue 5, Pages 1224-1234Publisher
WILEY
DOI: 10.1002/eji.200323825
Keywords
Leishmania; macrophage; nitric oxide synthase; phagocyte NADPH oxidase
Categories
Ask authors/readers for more resources
In the Leishmania major mouse model of cutaneous leishmaniasis inducible nitric oxide synthase (iNOS) is crucial for the killing of the parasite in the skin and draining lymph node. However, the effector mechanism operating against L. major in the spleen is unknown. As reactive oxygen intermediates might play a role, we analyzed macrophages and mice lacking the gp91phox subunit of the phagocyte NADPH oxidase (phox) for their ability to combat an infection with L. major. Macrophages from wild-type and gp91phox(-/-) mice had an equal capacity to kill L. major after activation by cytokines. Unlike iNOS, the activity of phox was dispensable for the resolution of the acute skin lesions and exerted only a limited effect on the containment of the parasites in the draining lymph node, but was essential for the clearance of L. major in the spleen. During the chronic phase of infection, parasites persisted at high levels in gp91phox(-/-) mice, and cutaneous lesions re-emerged in approximately 60% of these mice. gp91phox deficiency did not impair the expression of iNOS or the production of TNF and IFN-gamma. These results demonstrate that iNOS and phox are both required for the control of L. major in vivo and display unexpected organ- and stage-specific anti-leishmanial effects.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available