title: Blockade of TNF receptor 1 reduces disease severity but increases parasite transmission during Plasmodium chabaudi chabaudi infection.
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-alpha and lymphotoxin-alpha (LT-alpha), 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-alpha and LT-alpha 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.
authors.affiliation: Institutes of Evolution, Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, Scotland, UK. grainne.h.long@gmail.com
authors.forename: Gráinne H
authors.initials: GH
authors.lastname: Long
authors.forename: Brian H K
authors.initials: BH
authors.lastname: Chan
authors.forename: Judith E
authors.initials: JE
authors.lastname: Allen
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Read
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Graham
mesh_terms: D000818:Animals; D019353:Endemic Diseases; D005260:Female; D005838:Genotype; D006790:Host-Parasite Interactions; D006801:Humans; D008288:Malaria / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D011498:Protein Precursors; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; C061153:tumor necrosis factor precursor