Malaria systems immunology: Plasmodium vivax induces tolerance during primary infection through dysregulation of neutrophils and dendritic cells
Malaria systems immunology: Plasmodium vivax induces tolerance during primary infection through dysregulation of neutrophils and dendritic cells
Objectives
To dissect the transcriptional networks underpinning immune cells
responses during primary Plasmodium vivax infection of healthy
human adults.
Methods
We conducted network co-expression analysis of next-generation RNA
sequencing data from whole blood from P. vivax and P.
falciparum controlled human malaria infection (CHMI) of healthy naïve
and malaria-exposed volunteers. Single cell transcription signatures were used
to deconvolute the bulk RNA-Seq data into cell-specific signals.
Results
Initial exposure to P. vivax induced activation of
innate immunity, including efficient antigen presentation and complement
activation. However, this effect was accompanied by strong immunosuppression
mediated by dendritic cells via the induction of Indoleamine 2,3-Dioxygenase
1(IDO1) and Lymphocyte Activation Gene 3 (LAG3). Additionally, P. vivax induced
depletion of neutrophil populations associated with down regulation of
3G-protein coupled receptors, CRXCR1, CXCR2 and CSF3R. Accordingly, in
malaria-exposed volunteers the inflammatory response was attenuated, with a
decreased class II antigen presentation in dendritic cells. While the
immunosuppressive signalling was maintained between plasmodium species,
response to P. falciparum was significantly more immunogenic.
Conclusions
In silico analyses suggest that primary infection
with P. vivax induces potent immunosuppression mediated by
dendritic cells, conditioning subsequent anti-malarial immune responses.
Targeting immune evasion mechanisms could be an effective alternative for
improving vaccine efficacy.
malaria, , controlled human malaria infection, transcriptomics , dendritic cells (DC), immunoregulation, Vaccination
440-447
Vallejo Pulido, Andres
27bc0b94-0c40-4fd1-9533-7e267d588c0a
Read, Robert
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Arevalo-Herrera, Myriam
1a7e864f-13a1-451f-adf4-60c4797fb820
Herrera, Socrates
15ee87a3-93d7-4ff0-9bba-cf45a3b68756
Elliott, Timothy
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Polak, Marta
e0ac5e1a-7074-4776-ba23-490bd4da612d
November 2018
Vallejo Pulido, Andres
27bc0b94-0c40-4fd1-9533-7e267d588c0a
Read, Robert
b5caca7b-0063-438a-b703-7ecbb6fc2b51
Arevalo-Herrera, Myriam
1a7e864f-13a1-451f-adf4-60c4797fb820
Herrera, Socrates
15ee87a3-93d7-4ff0-9bba-cf45a3b68756
Elliott, Timothy
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Polak, Marta
e0ac5e1a-7074-4776-ba23-490bd4da612d
Vallejo Pulido, Andres, Read, Robert, Arevalo-Herrera, Myriam, Herrera, Socrates, Elliott, Timothy and Polak, Marta
(2018)
Malaria systems immunology: Plasmodium vivax induces tolerance during primary infection through dysregulation of neutrophils and dendritic cells.
Journal of Infection, 77 (5), .
(doi:10.1016/j.jinf.2018.09.005).
Abstract
Objectives
To dissect the transcriptional networks underpinning immune cells
responses during primary Plasmodium vivax infection of healthy
human adults.
Methods
We conducted network co-expression analysis of next-generation RNA
sequencing data from whole blood from P. vivax and P.
falciparum controlled human malaria infection (CHMI) of healthy naïve
and malaria-exposed volunteers. Single cell transcription signatures were used
to deconvolute the bulk RNA-Seq data into cell-specific signals.
Results
Initial exposure to P. vivax induced activation of
innate immunity, including efficient antigen presentation and complement
activation. However, this effect was accompanied by strong immunosuppression
mediated by dendritic cells via the induction of Indoleamine 2,3-Dioxygenase
1(IDO1) and Lymphocyte Activation Gene 3 (LAG3). Additionally, P. vivax induced
depletion of neutrophil populations associated with down regulation of
3G-protein coupled receptors, CRXCR1, CXCR2 and CSF3R. Accordingly, in
malaria-exposed volunteers the inflammatory response was attenuated, with a
decreased class II antigen presentation in dendritic cells. While the
immunosuppressive signalling was maintained between plasmodium species,
response to P. falciparum was significantly more immunogenic.
Conclusions
In silico analyses suggest that primary infection
with P. vivax induces potent immunosuppression mediated by
dendritic cells, conditioning subsequent anti-malarial immune responses.
Targeting immune evasion mechanisms could be an effective alternative for
improving vaccine efficacy.
Text
Malaria systems immunology
- Accepted Manuscript
Text
1-s2.0-S0163445318302780-main
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More information
Accepted/In Press date: 15 September 2018
e-pub ahead of print date: 22 September 2018
Published date: November 2018
Keywords:
malaria, , controlled human malaria infection, transcriptomics , dendritic cells (DC), immunoregulation, Vaccination
Identifiers
Local EPrints ID: 423692
URI: http://eprints.soton.ac.uk/id/eprint/423692
ISSN: 0163-4453
PURE UUID: c5026f2f-46e6-41c2-b14b-43ec1baf8837
Catalogue record
Date deposited: 27 Sep 2018 16:30
Last modified: 06 Jun 2024 04:06
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Contributors
Author:
Andres Vallejo Pulido
Author:
Myriam Arevalo-Herrera
Author:
Socrates Herrera
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