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CD4(+)T cells do not mediate within-host competition between genetically diverse malaria parasites

Barclay, Victoria C ; Råberg, Lars LU ; Chan, Brian H K ; Brown, Sheila ; Gray, David and Read, Andrew F (2008) In Royal Society of London. Proceedings B. Biological Sciences 275(1639). p.1171-1179
Abstract
Ecological interactions between microparasite populations in the same host are an important source of selection on pathogen traits such as virulence and drug resistance. In the rodent malaria model Plasmodium chabaudi in laboratory mice, parasites that are more virulent can competitively suppress less virulent parasites in mixed infections. There is evidence that some of this suppression is due to immune-mediated apparent competition, where an immune response elicited by one parasite population suppress the population density of another. This raises the question whether enhanced immunity following vaccination would intensify competitive interactions, thus strengthening selection for virulence in Plasmodium populations. Using the P.... (More)
Ecological interactions between microparasite populations in the same host are an important source of selection on pathogen traits such as virulence and drug resistance. In the rodent malaria model Plasmodium chabaudi in laboratory mice, parasites that are more virulent can competitively suppress less virulent parasites in mixed infections. There is evidence that some of this suppression is due to immune-mediated apparent competition, where an immune response elicited by one parasite population suppress the population density of another. This raises the question whether enhanced immunity following vaccination would intensify competitive interactions, thus strengthening selection for virulence in Plasmodium populations. Using the P. chabaudi model, we studied mixed infections of virulent and avirulent genotypes in CD4(+)T cell-depleted mice. Enhanced efficacy of CD4(+)T cell-dependent responses is the aim of several candidate malaria vaccines. We hypothesized that if immune-mediated interactions were involved in competition, removal of the CD4(+)T cells would alleviate competitive suppression of the avirulent parasite. Instead, we found no alleviation of competition in the acute phase, and significant enhancement of competitive suppression after parasite densities had peaked. Thus, the host immune response may actually be alleviating other forms of competition, such as that over red blood cells. Our results suggest that the CD4(+)-dependent immune response, and mechanisms that act to enhance it such as vaccination, may not have the undesirable affect of exacerbating within-host competition and hence the strength of this source of selection for virulence. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
competition, malaria, CD4(+)T cells
in
Royal Society of London. Proceedings B. Biological Sciences
volume
275
issue
1639
pages
1171 - 1179
publisher
Royal Society Publishing
external identifiers
  • wos:000254464000010
  • scopus:41649087356
  • pmid:18292054
ISSN
1471-2954
DOI
10.1098/rspb.2007.1713
language
English
LU publication?
yes
id
61c9a20f-fa63-4e2d-8dba-e2477f0b4e8a (old id 1182800)
date added to LUP
2016-04-01 14:34:14
date last changed
2024-02-25 16:19:36
@article{61c9a20f-fa63-4e2d-8dba-e2477f0b4e8a,
  abstract     = {{Ecological interactions between microparasite populations in the same host are an important source of selection on pathogen traits such as virulence and drug resistance. In the rodent malaria model Plasmodium chabaudi in laboratory mice, parasites that are more virulent can competitively suppress less virulent parasites in mixed infections. There is evidence that some of this suppression is due to immune-mediated apparent competition, where an immune response elicited by one parasite population suppress the population density of another. This raises the question whether enhanced immunity following vaccination would intensify competitive interactions, thus strengthening selection for virulence in Plasmodium populations. Using the P. chabaudi model, we studied mixed infections of virulent and avirulent genotypes in CD4(+)T cell-depleted mice. Enhanced efficacy of CD4(+)T cell-dependent responses is the aim of several candidate malaria vaccines. We hypothesized that if immune-mediated interactions were involved in competition, removal of the CD4(+)T cells would alleviate competitive suppression of the avirulent parasite. Instead, we found no alleviation of competition in the acute phase, and significant enhancement of competitive suppression after parasite densities had peaked. Thus, the host immune response may actually be alleviating other forms of competition, such as that over red blood cells. Our results suggest that the CD4(+)-dependent immune response, and mechanisms that act to enhance it such as vaccination, may not have the undesirable affect of exacerbating within-host competition and hence the strength of this source of selection for virulence.}},
  author       = {{Barclay, Victoria C and Råberg, Lars and Chan, Brian H K and Brown, Sheila and Gray, David and Read, Andrew F}},
  issn         = {{1471-2954}},
  keywords     = {{competition; malaria; CD4(+)T cells}},
  language     = {{eng}},
  number       = {{1639}},
  pages        = {{1171--1179}},
  publisher    = {{Royal Society Publishing}},
  series       = {{Royal Society of London. Proceedings B. Biological Sciences}},
  title        = {{CD4(+)T cells do not mediate within-host competition between genetically diverse malaria parasites}},
  url          = {{http://dx.doi.org/10.1098/rspb.2007.1713}},
  doi          = {{10.1098/rspb.2007.1713}},
  volume       = {{275}},
  year         = {{2008}},
}