Distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of leishmania donovani infection

Engwerda, Christian R., Ato, Manabu, Stäger, Simona, Alexander, Clare E., Stanley, Amanda C. and Kaye, Paul M. (2004) Distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of leishmania donovani infection. American Journal of Pathology, 165 6: 2123-2133. doi:10.1016/S0002-9440(10)63262-2

Author Engwerda, Christian R.
Ato, Manabu
Stäger, Simona
Alexander, Clare E.
Stanley, Amanda C.
Kaye, Paul M.
Title Distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of leishmania donovani infection
Formatted title
Distinct roles for lymphotoxin-α and tumor necrosis factor in the control of Leishmania donovani infection
Journal name American Journal of Pathology   Check publisher's open access policy
ISSN 0002-9440
Publication date 2004-12
Sub-type Article (original research)
DOI 10.1016/S0002-9440(10)63262-2
Volume 165
Issue 6
Start page 2123
End page 2133
Total pages 11
Place of publication Birmingham, AL., U.S.
Publisher American Society for Investigative Pathology
Language eng
Subject 11 Medical and Health Sciences
1103 Clinical Sciences
Formatted abstract
Tumor necrosis factor (TNF) is critical for the control of visceral leishmaniasis caused by Leishmania donovani. However, the role of the related cytokine lymphotoxin (LT) α in this infection is unknown. Here we report that C57BL/6 mice deficient in TNF (B6.TNF–/–) or LTα (B6.LTα–/–) have increased susceptibility to hepatic L. donovani infection. Furthermore, the outcome of infection in bone marrow chimeric mice is dependent on donor hematopoietic cells, indicating that developmental defects in lymphoid organs were not responsible for increased susceptibility to L. donovani. Although both LTα and TNF regulated the migration of leukocytes into the sinusoidal area of the infected liver, their roles were distinct. LTα was essential for migration of leukocytes from periportal areas, an event consistent with LTα-dependent up-regulation of VCAM-1 on liver sinusoid lining cells, whereas TNF was essential for leukocyte recruitment to the liver. During visceral leishmaniasis, both cytokines were produced by radio-resistant cells and by CD4+ T cells. LTα and TNF production by the former was required for granuloma assembly, while production of these cytokines by CD4+ T cells was necessary to control parasite growth. The production of inducible nitric oxide synthase was also found to be deficient in TNF- and LTα-deficient infected mice. These results demonstrate that both LTα and TNF are required for control of L. donovani infection in noncompensatory ways.
Copyright © American Society for Investigative Pathology
Keyword Cytokine
Lymphotoxin α
Anatomic pathology
Leishmania donovani
Tumor necrosis factor α
Tumor necrosis factor alpha
Lymphotoxin alpha
Q-Index Code C1
Additional Notes Published under "Immunopathology and Infectious Disease"

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Public Health Publications
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