Blockade of TNF receptor 1 reduces disease severity but increases parasite transmission during Plasmodium chabaudi chabaudi infection

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

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Reducing host carriage of transmission-stage malaria parasites (gametocytes) is expected to decrease the population-wide burden of malaria. Some malaria disease severity is attributed to the induction of the pro-inflammatory cytokines TNF-α and lymphotoxin-alpha (LT-α), and we are interested in whether anti-malaria interventions which ameliorate the symptoms induced by those cytokines may have the capacity to alter malaria transmission. As many functions of TNF-α and LT-α are exerted through TNF receptor 1 (TNFR1), we investigated the effect TNFR1 blockade exerted on parasite transmission using the rodent malaria Plasmodium chabaudi chabaudi. We found that blocking TNFR1 simultaneously increased gametocyte density and infectivity to mosquitoes, whilst reducing disease severity (weight loss). These transmission-enhancing and severity-reducing effects of TNFR1 blockade were independent of asexual parasite load and were observed for several P. c. chabaudi genotypes. These results suggest that the effects of candidate malaria interventions on infectivity should be examined alongside effects on disease severity so that the epidemiological consequences of such interventions can be evaluated.

Original languageEnglish (US)
Pages (from-to)1073-1081
Number of pages9
JournalInternational Journal for Parasitology
Volume38
Issue number8-9
DOIs
StatePublished - Jul 1 2008

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Infectious Diseases

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