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

Yaw Bediako; Rhys Adams; Adam J. Reid; John Joseph Valletta; Francis M. Ndungu; Jan Sodenkamp; Jedidah Mwacharo; Joyce Mwongeli Ngoi; Domtila Kimani; Oscar Kai; Juliana Wambua; George Nyangweso; Etienne P. De Villiers; Mandy Sanders; Magda Ewa Lotkowska; Jing Wen Lin; Sarah Manni; John W.G. Addy; Mario Recker; Chris Newbold; Matthew Berriman; Philip Bejon; Kevin Marsh; Jean Langhorne

doi:10.1186/s12916-019-1292-y

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

Yaw Bediako, Rhys Adams, Adam J. Reid, John Joseph Valletta, Francis M. Ndungu, Jan Sodenkamp, Jedidah Mwacharo, Joyce Mwongeli Ngoi, Domtila Kimani, Oscar Kai, Juliana Wambua, George Nyangweso, Etienne P. De Villiers, Mandy Sanders, Magda Ewa Lotkowska, Jing Wen Lin, Sarah Manni, John W.G. Addy, Mario Recker, Chris NewboldMatthew Berriman, Philip Bejon, Kevin Marsh, Jean Langhorne^*

^*Corresponding author for this work

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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.

Original language	English
Article number	60
Number of pages	14
Journal	BMC Medicine
Volume	17
DOIs	https://doi.org/10.1186/s12916-019-1292-y
Publication status	Published - 13 Mar 2019

Keywords

Immune activation
Malaria
Systems immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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.
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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., ... Langhorne, J. (2019). Repeated clinical malaria episodes are associated with modification of the immune system in children. BMC Medicine, 17, Article 60. https://doi.org/10.1186/s12916-019-1292-y

@article{381f16cc40a8415281c50036043cc8f5,

title = "Repeated clinical malaria episodes are associated with modification of the immune system in children",

abstract = "BackgroundThere 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.MethodsWe 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).ResultsWe 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.ConclusionTranscriptomic 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.",

keywords = "Immune activation, Malaria, Systems immunology",

author = "Yaw Bediako and Rhys Adams and Reid, {Adam J.} and Valletta, {John Joseph} and Ndungu, {Francis M.} and Jan Sodenkamp and Jedidah Mwacharo and Ngoi, {Joyce Mwongeli} and Domtila Kimani and Oscar Kai and Juliana Wambua and George Nyangweso and {De Villiers}, {Etienne P.} and Mandy Sanders and Lotkowska, {Magda Ewa} and Lin, {Jing Wen} and Sarah Manni and Addy, {John W.G.} and Mario Recker and Chris Newbold and Matthew Berriman and Philip Bejon and Kevin Marsh and Jean Langhorne",

note = "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).",

year = "2019",

month = mar,

day = "13",

doi = "10.1186/s12916-019-1292-y",

language = "English",

volume = "17",

journal = "BMC Medicine",

issn = "1741-7015",

publisher = "Wiley-Blackwell",

}

Bediako, Y, Adams, R, Reid, AJ, Valletta, JJ, Ndungu, FM, Sodenkamp, J, Mwacharo, J, Ngoi, JM, Kimani, D, Kai, O, Wambua, J, Nyangweso, G, De Villiers, EP, Sanders, M, Lotkowska, ME, Lin, JW, Manni, S, Addy, JWG, 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

TY - JOUR

T1 - Repeated clinical malaria episodes are associated with modification of the immune system in children

AU - Bediako, Yaw

AU - Adams, Rhys

AU - Reid, Adam J.

AU - Valletta, John Joseph

AU - Ndungu, Francis M.

AU - Sodenkamp, Jan

AU - Mwacharo, Jedidah

AU - Ngoi, Joyce Mwongeli

AU - Kimani, Domtila

AU - Kai, Oscar

AU - Wambua, Juliana

AU - Nyangweso, George

AU - De Villiers, Etienne P.

AU - Sanders, Mandy

AU - Lotkowska, Magda Ewa

AU - Lin, Jing Wen

AU - Manni, Sarah

AU - Addy, John W.G.

AU - Recker, Mario

AU - Newbold, Chris

AU - Berriman, Matthew

AU - Bejon, Philip

AU - Marsh, Kevin

AU - Langhorne, Jean

N1 - 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).

PY - 2019/3/13

Y1 - 2019/3/13

N2 - BackgroundThere 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.MethodsWe 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).ResultsWe 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.ConclusionTranscriptomic 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.

AB - BackgroundThere 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.MethodsWe 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).ResultsWe 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.ConclusionTranscriptomic 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.

KW - Immune activation

KW - Malaria

KW - Systems immunology

U2 - 10.1186/s12916-019-1292-y

DO - 10.1186/s12916-019-1292-y

M3 - Article

C2 - 30862316

AN - SCOPUS:85062878891

SN - 1741-7015

VL - 17

JO - BMC Medicine

JF - BMC Medicine

M1 - 60

ER -

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

Abstract

Keywords

UN SDGs

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