UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria

Engwerda, CR; Mynott, TL; Sawhney, S; De Souza, JB; Bickle, QD; Kaye, PM; (2002) Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria. J EXP MED , 195 (10) 1371 - 1377. 10.1084/jem.20020128. Green open access

[img]
Preview
PDF
6943.pdf

Download (180kB)

Abstract

Cerebral malaria (CM) causes death in children and nonimmune adults. TNF-alpha has been thought to play a key role in the development of CM. In contrast, the role of the related cytokine lymphotoxin alpha (LTalpha) in CM has been overlooked. Here we show that LTalpha, not TNFalpha, is the principal mediator of murine CM. Mice deficient in TNFalpha (B6.TNFalpha(-/-)) were as susceptible to CM caused by Plasmodium berghei (ANKA) as C57BL/6 mice, and died 6 to 8 d after infection after developing neurological signs of CM, associated with perivascular brain hemorrhage. Significantly, the development of CM in B6.TNFalpha(-/-) mice was not associated with increased intracellular adhesion molecule (ICAM)-1 expression on cerebral vasculature and the intraluminal accumulation of complement receptor 3 (CR3)-positive leukocytes was moderate. In contrast, mice deficient in-LTalpha (B6.LTalpha(-/-)) were completely resistant to CM and died 11 to 14 d after infection with severe anemia and hyperparasitemia. No difference in blood parasite burden was found between C57BL/6, B6.TNFalpha(- /-) and B6.LTalpha(-/-) mice at the onset of CM symptoms in the two susceptible strains. In addition, studies in bone marrow (BM) chimeric mice showed the persistence of cerebral LTalpha mRNA after irradiation and engraftment of LTalpha-deficient BM, indicating that LTalpha originated from a radiation-resistant cell population.

Type: Article
Title: Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria
Open access status: An open access version is available from UCL Discovery
DOI: 10.1084/jem.20020128
Keywords: parasitic disease, protozoan infection, Plasmodium berghei, immunopathology, infection, INTERCELLULAR-ADHESION MOLECULE-1, LEISHMANIA-DONOVANI INFECTION, MONOCLONAL-ANTIBODY, FALCIPARUM-MALARIA, DEFICIENT MICE, SCID MICE, TNF, LEUKOCYTE, IMMUNOPATHOLOGY, EXPRESSION
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/6943
Downloads since deposit
188Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item