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Parasite genetic diversity does not influence TNF-mediated effects on the virulence of primary

Summary: Parasite genetic diversity does not influence
TNF-mediated effects on the virulence of primary
rodent malaria infections
G. H. LONG*, B. H. K. CHAN, J. E. ALLEN, A. F. READ and A. L. GRAHAM
Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh,
King's Buildings, West Mains Road, Edinburgh EH9 3JT, Scotland
(Received 3 April 2006; revised 17 June 2006; accepted 21 June 2006)
The pro-inflammatory cytokine tumour necrosis factor alpha (TNF-a) is associated with malaria virulence (disease
severity) in both rodents and humans. We are interested in whether parasite genetic diversity influences TNF-mediated
effects on malaria virulence. Here, primary infections with genetically distinct Plasmodium chabaudi chabaudi (P.c.c.) clones
varied in the virulence and cytokine responses induced in female C57BL/6 mice. Even when parasitaemia was controlled
for, a greater day 7 TNF-a response was induced by infection with more virulent P.c.c. clones. Since many functions of
TNF-a are exerted through TNF receptor 1 (TNFR1), a TNFR-1 fusion protein (TNFR-Ig) was used to investigate
whether TNFR1 blockade eliminated clone virulence differences. We found that TNFR-1 blockade ameliorated the
weight loss but not the anaemia induced by malaria infection, regardless of P.c.c. clone. We show that distinct P.c.c.
infections induced significantly different plasma interferon gamma (IFN-c), interleukin 6 (IL-6) and interleukin 10
(IL-10) levels. Our results demonstrate that regardless of P.c.c. genotype, blocking TNFR1 signalling protected against
weight loss, but had negligible effects on both anaemia and asexual parasite kinetics. Thus, during P.c.c. infection, TNF-a
is a key mediator of weight loss, independent of parasite load and across parasite genotypes.


Source: Allen, Judith - School of Biological Sciences, University of Edinburgh
Read, Andrew - Center for Infectious Disease Dynamics & Department of Entomology, Pennsylvania State University


Collections: Biology and Medicine; Environmental Sciences and Ecology