| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
in Remodeling the Splenic Marginal Zone during Leishmania donovani Infection
From the Department of Infectious and Tropical Diseases,*London School of Hygiene and Tropical Medicine, London; and the Centre for Molecular Microbiology and Infection,Imperial College of Science, Technology, and Medicine, London, United Kingdom
The development of secondary lymphoid organs is a highly regulated process, mediated by tumor necrosis factor (TNF) family cytokines. In contrast, the mechanisms controlling changes in lymphoid architecture that occur during infectious disease are poorly understood. Here we demonstrate that during infection with Leishmania donovani, the marginal zone of mice undergoes extensive remodeling, similar in extent to developmental abnormalities in mice lacking some TNF family cytokines. This process is selective, comprising a dramatic and rapid loss of marginal zone macrophages (MZMs). As a functional consequence, lymphocyte traffic into the white pulp is impaired during chronic leishmaniasis. Significantly, MZMs were preserved in L. donovani-infected B6.TNF-
-/- mice or mice that received anti-TNF- antibodies, whereas studies in CD8+ T-cell-deficient mice and in mice lacking functional CD95L, excluded a direct role for either cytotoxic T lymphocyte activity or CD95-mediated apoptosis in this process. Loss of MZMs was independent of parasite burden, yet could be partially prevented by chemotherapy, which in turn reduced endogenous TNF- levels. This is the first report of an infectious agent causing selective and long-lasting changes to the marginal zone via TNF--mediated mechanisms, and illustrates that those cytokines involved in establishing lymphoid architecture during development, may also play a role in infection-induced lymphoid tissue remodeling.
Related articles in Am J Pathol:
This article has been cited by other articles:
 |
|
 |
|
  E. T. Cadman, A. Y. Abdallah, C. Voisine, A.-M. Sponaas, P. Corran, T. Lamb, D. Brown, F. Ndungu, and J. Langhorne Alterations of Splenic Architecture in Malaria Are Induced Independently of Toll-Like Receptors 2, 4, and 9 or MyD88 and May Affect Antibody Affinity Infect. Immun., September 1, 2008; 76(9): 3924 - 3931. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Nolte and R. A.W. van Lier The price of the CD27-CD70 costimulatory axis: you can't have it all J. Exp. Med., October 30, 2006; 203(11): 2405 - 2408. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Matter, B. Odermatt, H. Yagita, J.-M. Nuoffer, and A. F. Ochsenbein Elimination of chronic viral infection by blocking CD27 signaling J. Exp. Med., September 4, 2006; 203(9): 2145 - 2155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Beattie, C. R. Engwerda, M. Wykes, and M. F. Good CD8+ T Lymphocyte-Mediated Loss of Marginal Metallophilic Macrophages following Infection with Plasmodium chabaudi chabaudi AS J. Immunol., August 15, 2006; 177(4): 2518 - 2526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Krucken, L. I. Mehnert, M. A. Dkhil, M. El-Khadragy, W. P. M. Benten, H. Mossmann, and F. Wunderlich Massive Destruction of Malaria-Parasitized Red Blood Cells despite Spleen Closure Infect. Immun., October 1, 2005; 73(10): 6390 - 6398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Engwerda, M. Ato, S. Stager, C. E. Alexander, A. C. Stanley, and P. M. Kaye Distinct Roles for Lymphotoxin-{alpha} and Tumor Necrosis Factor in the Control of Leishmania donovani Infection Am. J. Pathol., December 1, 2004; 165(6): 2123 - 2133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ato, H. Nakano, T. Kakiuchi, and P. M. Kaye Localization of Marginal Zone Macrophages Is Regulated by C-C Chemokine Ligands 21/19 J. Immunol., October 15, 2004; 173(8): 4815 - 4820. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
