Experimental manipulation of immune-mediated disease and its fitness costs for rodent malaria parasites

Gráinne H. Long, Brian H.K. Chan, Judith E. Allen, Andrew F. Read, Andrea L. Graham

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background. Explaining parasite virulence (harm to the host) represents a major challenge for evolutionary and biomedical scientists alike. Most theoretical models of virulence evolution assume that virulence arises as a direct consequence of host exploitation, the process whereby parasites convert host resources into transmission opportunities. However, infection-induced disease can be immune-mediated (immunopathology). Little is known about how immunopathology affects parasite fitness, or how it will affect the evolution of parasite virulence. Here we studied the effects of immunopathology on infection-induced host mortality rate and lifetime transmission potential - key components of parasite fitness - using the rodent malaria model, Plasmodium chabaudi chabaudi. Results. Neutralizing interleukin [IL]-10, an important regulator of inflammation, allowed us to experimentally increase the proportion of virulence due to immunopathology for eight parasite clones. In vivo blockade of the IL-10 receptor (IL-10R) with a neutralizing antibody resulted in a shorter time to death that was independent of parasite density and was particularly marked for normally avirulent clones. This suggests that IL-10 induction may provide a pathway to avirulence for P. c. chabaudi. Despite the increased investment in transmission-stage parasites observed for some clones in response to IL-10R blockade, experimental enhancement of immunopathology incurred a uniform fitness cost to all parasite clones by reducing lifetime transmission potential. Conclusion. This is the first experimental study to demonstrate that infection-induced immunopathology and parasite genetic variability may together have the potential to shape virulence evolution. In accord with recent theory, the data show that some forms of immunopathology may select for parasites that make hosts less sick.

Original languageEnglish (US)
Article number128
JournalBMC Evolutionary Biology
Volume8
Issue number1
DOIs
StatePublished - May 29 2008

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malaria
rodent
immunopathology
parasite
fitness
rodents
parasites
virulence
cost
clone
interleukin-10
clones
infection
interleukins
neutralizing antibodies
neutralization
antibody
experimental study
inflammation
death

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics

Cite this

Long, Gráinne H. ; Chan, Brian H.K. ; Allen, Judith E. ; Read, Andrew F. ; Graham, Andrea L. / Experimental manipulation of immune-mediated disease and its fitness costs for rodent malaria parasites. In: BMC Evolutionary Biology. 2008 ; Vol. 8, No. 1.
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Experimental manipulation of immune-mediated disease and its fitness costs for rodent malaria parasites. / Long, Gráinne H.; Chan, Brian H.K.; Allen, Judith E.; Read, Andrew F.; Graham, Andrea L.

In: BMC Evolutionary Biology, Vol. 8, No. 1, 128, 29.05.2008.

Research output: Contribution to journalArticle

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