|
|
|
|
|
|
|
||
J. Exp. Med.,
Volume 189, Number 4, February 15, 1999 741-746
By
From the * Department of Medicine and the To determine the relative contributions of respiratory burst-derived reactive oxygen intermediates (ROI) versus reactive nitrogen intermediates (RNI) to macrophage-mediated intracellular host defense, mice genetically deficient in these mechanisms were challenged with Leishmania donovani, a protozoan that selectively parasitizes visceral tissue macrophages. During the
early stage of liver infection at wk 2, both respiratory burst-deficient gp91phox Beatrice and Samuel Seaver Laboratory, Division of
Hematology-Oncology, Cornell University Medical College, New York 10021
/ (X-linked
chronic granulomatous disease [X-CGD]) mice and inducible nitric oxide synthase (iNOS)
knockout (KO) mice displayed comparably increased susceptibility. Thereafter, infection was
unrestrained in mice lacking iNOS but was fully controlled in X-CGD mice. Mononuclear cell influx into infected liver foci in X-CGD and iNOS KO mice was also overtly impaired at
wk 2. However, granuloma assembly in parasitized tissue eventually developed in both hosts
but with divergent effects: mature granulomas were functionally active (leishmanicidal) in
X-CGD mice but inert in iNOS-deficient animals. These results suggest that (a) ROI and RNI
probably act together in the early stage of intracellular infection to regulate both tissue recruitment of mononuclear inflammatory cells and the initial extent of microbial replication, (b)
RNI alone are necessary and sufficient for eventual control of visceral infection, and (c) although mature granulomas have traditionally been associated with control of such infections,
these structures fail to limit intracellular parasite replication in the absence of iNOS.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
