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A role for tumor necrosis factor-alpha in remodeling the splenic marginal zone during Leishmania donovani infection.
- Source :
-
The American journal of pathology [Am J Pathol] 2002 Aug; Vol. 161 (2), pp. 429-37. - Publication Year :
- 2002
-
Abstract
- 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-alpha(-/-) mice or mice that received anti-TNF-alpha 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-alpha levels. This is the first report of an infectious agent causing selective and long-lasting changes to the marginal zone via TNF-alpha-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.
- Subjects :
- Animals
Cell Death genetics
Leishmaniasis, Visceral genetics
Macrophages pathology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Spleen metabolism
Tumor Necrosis Factor-alpha genetics
Leishmania donovani
Leishmaniasis, Visceral metabolism
Leishmaniasis, Visceral pathology
Spleen pathology
Tumor Necrosis Factor-alpha deficiency
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9440
- Volume :
- 161
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 12163368
- Full Text :
- https://doi.org/10.1016/s0002-9440(10)64199-5