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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-03-13

AUTHORS

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

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. More... »

PAGES

60

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12916-019-1292-y

DOI

http://dx.doi.org/10.1186/s12916-019-1292-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112712529

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30862316


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24 schema:description 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.
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