Antigenic Variation in Malaria
Involves a Highly Structured Switching Pattern
Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through
an immune evasion strategy known as antigenic variation. In the human malaria
parasite Plasmodium falciparum, this involves transcriptional
switching among members of the var gene family, causing
parasites with different antigenic and phenotypic characteristics to appear at
different times within a population. Here we use a genome-wide approach to
explore this process in vitro within a set of cloned parasite
populations. Our analyses reveal a non-random, highly structured switch pathway
where an initially dominant transcript switches via a set of
switch-intermediates either to a new dominant transcript, or back to the
original. We show that this specific pathway can arise through an evolutionary
conflict in which the pathogen has to optimise between safeguarding its limited
antigenic repertoire and remaining capable of establishing infections in
non-naïve individuals. Our results thus demonstrate a crucial role for
structured switching during the early phases of infections and provide a
unifying theory of antigenic variation in P. falciparum malaria
as a balanced process of parasite-intrinsic switching and immune-mediated
selection.
Vyšlo v časopise:
Antigenic Variation in Malaria
Involves a Highly Structured Switching Pattern. PLoS Pathog 7(3): e32767. doi:10.1371/journal.ppat.1001306
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1001306
Souhrn
Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through
an immune evasion strategy known as antigenic variation. In the human malaria
parasite Plasmodium falciparum, this involves transcriptional
switching among members of the var gene family, causing
parasites with different antigenic and phenotypic characteristics to appear at
different times within a population. Here we use a genome-wide approach to
explore this process in vitro within a set of cloned parasite
populations. Our analyses reveal a non-random, highly structured switch pathway
where an initially dominant transcript switches via a set of
switch-intermediates either to a new dominant transcript, or back to the
original. We show that this specific pathway can arise through an evolutionary
conflict in which the pathogen has to optimise between safeguarding its limited
antigenic repertoire and remaining capable of establishing infections in
non-naïve individuals. Our results thus demonstrate a crucial role for
structured switching during the early phases of infections and provide a
unifying theory of antigenic variation in P. falciparum malaria
as a balanced process of parasite-intrinsic switching and immune-mediated
selection.
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Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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