St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  •   St Andrews Research Repository
  • University of St Andrews Research
  • University of St Andrews Research
  • University of St Andrews Research
  • View Item
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

Repeated clinical malaria episodes are associated with modification of the immune system in children

Thumbnail
View/Open
Bediako_2019_BMCM_Repeated_CC.pdf (1.797Mb)
Date
13/03/2019
Author
Bediako, Yaw
Adams, Rhys
Reid, Adam J.
Valletta, John Joseph
Ndungu, Francis M.
Sodenkamp, Jan
Mwacharo, Jedidah
Ngoi, Joyce Mwongeli
Kimani, Domtila
Kai, Oscar
Wambua, Juliana
Nyangweso, George
De Villiers, Etienne P.
Sanders, Mandy
Lotkowska, Magda Ewa
Lin, Jing Wen
Manni, Sarah
Addy, John W.G.
Recker, Mario
Newbold, Chris
Berriman, Matthew
Bejon, Philip
Marsh, Kevin
Langhorne, Jean
Keywords
Immune activation
Malaria
Systems immunology
QR180 Immunology
E-NDAS
Metadata
Show full item record
Altmetrics Handle Statistics
Altmetrics DOI Statistics
Abstract
Background There are over 200 million reported cases of malaria each year, and most children living in endemic areas will experience multiple episodes of clinical disease before puberty. We set out to understand how frequent clinical malaria, which elicits a strong inflammatory response, affects the immune system and whether these modifications are observable in the absence of detectable parasitaemia. Methods We used a multi-dimensional approach comprising whole blood transcriptomic, cellular and plasma cytokine analyses on a cohort of children living with endemic malaria, but uninfected at sampling, who had been under active surveillance for malaria for 8 years. Children were categorised into two groups depending on the cumulative number of episodes experienced: high (≥ 8) or low (< 5). Results We observe that multiple episodes of malaria are associated with modification of the immune system. Children who had experienced a large number of episodes demonstrated upregulation of interferon-inducible genes, a clear increase in circulating levels of the immunoregulatory cytokine IL-10 and enhanced activation of neutrophils, B cells and CD8+ T cells. Conclusion Transcriptomic analysis together with cytokine and immune cell profiling of peripheral blood can robustly detect immune differences between children with different numbers of prior malaria episodes. Multiple episodes of malaria are associated with modification of the immune system in children. Such immune modifications may have implications for the initiation of subsequent immune responses and the induction of vaccine-mediated protection.
Citation
Bediako , Y , Adams , R , Reid , A J , Valletta , J J , Ndungu , F M , Sodenkamp , J , Mwacharo , J , Ngoi , J M , Kimani , D , Kai , O , Wambua , J , Nyangweso , G , De Villiers , E P , Sanders , M , Lotkowska , M E , Lin , J W , Manni , S , Addy , J W G , Recker , M , Newbold , C , Berriman , M , Bejon , P , Marsh , K & Langhorne , J 2019 , ' Repeated clinical malaria episodes are associated with modification of the immune system in children ' , BMC Medicine , vol. 17 , 60 . https://doi.org/10.1186/s12916-019-1292-y
Publication
BMC Medicine
Status
Peer reviewed
DOI
https://doi.org/10.1186/s12916-019-1292-y
ISSN
1741-7015
Type
Journal article
Rights
Copyright © The Author(s). 2019 Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Description
The study received funding from the UK Medical Research Council, (MRC Programme grant #: MR/M003906/1). MB and AR are supported by the Wellcome Trust (Grant #: WT 206194).
Collections
  • University of St Andrews Research
URI
http://hdl.handle.net/10023/20153

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter