Faster growth with shorter antigens can explain a VSG hierarchy during African trypanosome infections: a feint attack by parasites

Dianbo Liu (Lead / Corresponding author), Luca Albergante, Timothy Newman, David Horn (Lead / Corresponding author)

Research output: Contribution to journalArticle

1 Citation (Scopus)
83 Downloads (Pure)

Abstract

The parasitic African trypanosome, Trypanosoma brucei, evades the adaptive host immune response by a process of antigenic variation that involves the clonal switching of variant surface glycoproteins (VSGs). The VSGs that come to dominate in vivo during an infection are not entirely random, but display a hierarchical order. How this arises is not fully understood. Combining available genetic data with mathematical modelling, we report a VSG-length-dependent hierarchical timing of clonal VSG dominance in a mouse model, consistent with an inverse correlation between VSG length and trypanosome growth-rate. Our analyses indicate that, among parasites switching to new VSGs, those expressing shorter VSGs preferentially accumulate to a detectable level that is sufficient to trigger a targeted immune response. This may be due to the increased metabolic cost of producing longer VSGs. Subsequent elimination of faster-growing parasites then allows slower-growing parasites with longer VSGs to accumulate. This interaction between the host and parasite is able to explain the temporal distribution of VSGs observed in vivo. Thus, our findings reveal a length-dependent hierarchy that operates during T. brucei infection. This represents a ‘feint attack’ diversion tactic utilised by these persistent parasites to out-maneuver the host adaptive immune system.
Original languageEnglish
Article number10922
Pages (from-to)1-10
Number of pages10
JournalScientific Reports
Volume8
Early online date19 Jul 2018
DOIs
Publication statusPublished - 2018

Fingerprint

Trypanosomiasis
Membrane Glycoproteins
Parasites
Antigens
Growth
Infection
Trypanosoma brucei brucei
Antigenic Variation
Host-Parasite Interactions
Adaptive Immunity
Immune System
Costs and Cost Analysis

Cite this

@article{2d0470982a24495cb8d97dfec6c18039,
title = "Faster growth with shorter antigens can explain a VSG hierarchy during African trypanosome infections: a feint attack by parasites",
abstract = "The parasitic African trypanosome, Trypanosoma brucei, evades the adaptive host immune response by a process of antigenic variation that involves the clonal switching of variant surface glycoproteins (VSGs). The VSGs that come to dominate in vivo during an infection are not entirely random, but display a hierarchical order. How this arises is not fully understood. Combining available genetic data with mathematical modelling, we report a VSG-length-dependent hierarchical timing of clonal VSG dominance in a mouse model, consistent with an inverse correlation between VSG length and trypanosome growth-rate. Our analyses indicate that, among parasites switching to new VSGs, those expressing shorter VSGs preferentially accumulate to a detectable level that is sufficient to trigger a targeted immune response. This may be due to the increased metabolic cost of producing longer VSGs. Subsequent elimination of faster-growing parasites then allows slower-growing parasites with longer VSGs to accumulate. This interaction between the host and parasite is able to explain the temporal distribution of VSGs observed in vivo. Thus, our findings reveal a length-dependent hierarchy that operates during T. brucei infection. This represents a ‘feint attack’ diversion tactic utilised by these persistent parasites to out-maneuver the host adaptive immune system.",
author = "Dianbo Liu and Luca Albergante and Timothy Newman and David Horn",
note = "This work was supported by a Wellcome Trust PhD studentship to D.L. D.H. is supported by a Wellcome Trust Senior Investigator Award (100320/Z/12/Z). L.A. and T.N. acknowledge support from the Scottish Universities Life Sciences Alliance. Funding for open access charge: Wellcome Trust.",
year = "2018",
doi = "10.1038/s41598-018-29296-8",
language = "English",
volume = "8",
pages = "1--10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

Faster growth with shorter antigens can explain a VSG hierarchy during African trypanosome infections : a feint attack by parasites. / Liu, Dianbo (Lead / Corresponding author); Albergante, Luca; Newman, Timothy; Horn, David (Lead / Corresponding author).

In: Scientific Reports, Vol. 8, 10922, 2018, p. 1-10.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Faster growth with shorter antigens can explain a VSG hierarchy during African trypanosome infections

T2 - a feint attack by parasites

AU - Liu, Dianbo

AU - Albergante, Luca

AU - Newman, Timothy

AU - Horn, David

N1 - This work was supported by a Wellcome Trust PhD studentship to D.L. D.H. is supported by a Wellcome Trust Senior Investigator Award (100320/Z/12/Z). L.A. and T.N. acknowledge support from the Scottish Universities Life Sciences Alliance. Funding for open access charge: Wellcome Trust.

PY - 2018

Y1 - 2018

N2 - The parasitic African trypanosome, Trypanosoma brucei, evades the adaptive host immune response by a process of antigenic variation that involves the clonal switching of variant surface glycoproteins (VSGs). The VSGs that come to dominate in vivo during an infection are not entirely random, but display a hierarchical order. How this arises is not fully understood. Combining available genetic data with mathematical modelling, we report a VSG-length-dependent hierarchical timing of clonal VSG dominance in a mouse model, consistent with an inverse correlation between VSG length and trypanosome growth-rate. Our analyses indicate that, among parasites switching to new VSGs, those expressing shorter VSGs preferentially accumulate to a detectable level that is sufficient to trigger a targeted immune response. This may be due to the increased metabolic cost of producing longer VSGs. Subsequent elimination of faster-growing parasites then allows slower-growing parasites with longer VSGs to accumulate. This interaction between the host and parasite is able to explain the temporal distribution of VSGs observed in vivo. Thus, our findings reveal a length-dependent hierarchy that operates during T. brucei infection. This represents a ‘feint attack’ diversion tactic utilised by these persistent parasites to out-maneuver the host adaptive immune system.

AB - The parasitic African trypanosome, Trypanosoma brucei, evades the adaptive host immune response by a process of antigenic variation that involves the clonal switching of variant surface glycoproteins (VSGs). The VSGs that come to dominate in vivo during an infection are not entirely random, but display a hierarchical order. How this arises is not fully understood. Combining available genetic data with mathematical modelling, we report a VSG-length-dependent hierarchical timing of clonal VSG dominance in a mouse model, consistent with an inverse correlation between VSG length and trypanosome growth-rate. Our analyses indicate that, among parasites switching to new VSGs, those expressing shorter VSGs preferentially accumulate to a detectable level that is sufficient to trigger a targeted immune response. This may be due to the increased metabolic cost of producing longer VSGs. Subsequent elimination of faster-growing parasites then allows slower-growing parasites with longer VSGs to accumulate. This interaction between the host and parasite is able to explain the temporal distribution of VSGs observed in vivo. Thus, our findings reveal a length-dependent hierarchy that operates during T. brucei infection. This represents a ‘feint attack’ diversion tactic utilised by these persistent parasites to out-maneuver the host adaptive immune system.

UR - http://www.scopus.com/inward/record.url?scp=85050593449&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-29296-8

DO - 10.1038/s41598-018-29296-8

M3 - Article

C2 - 30026531

VL - 8

SP - 1

EP - 10

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 10922

ER -