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

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

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 languageEnglish
Article number60
Number of pages14
JournalBMC Medicine
Volume17
DOIs
Publication statusPublished - 13 Mar 2019

Keywords

  • Immune activation
  • Malaria
  • Systems immunology

Fingerprint

Dive into the research topics of 'Repeated clinical malaria episodes are associated with modification of the immune system in children'. Together they form a unique fingerprint.

Cite this