Both inflammatory and regulatory cytokine responses to malaria are blunted with increasing age in highly exposed children

Malaria Journal

Research

Prasanna Jagannathan¹  Grant Dorsey²  Lila Farrington²  Hilary Vance²  Margaret E. Feeney³  Mary Prahl⁴  Agaba Katureebe⁵  John Rek⁵  Emmanuel Arinaitwe⁵  Moses R. Kamya⁶ 

[1] Department of Medicine, Stanford University, Stanford, CA, USA;Department of Medicine, University of California San Francisco, San Francisco, CA, USA;Department of Medicine, University of California San Francisco, San Francisco, CA, USA;Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA;Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA;Infectious Diseases Research Collaboration, Kampala, Uganda;Infectious Diseases Research Collaboration, Kampala, Uganda;Makerere University College of Health Sciences, Kampala, Uganda;

关键词: Cytokines;    Malaria;    Tolerance;    Immunity;    Age;   

DOI  :  10.1186/s12936-017-2148-6

 received in 2017-08-25, accepted in 2017-12-19,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundYoung children are at greatest risk for malaria-associated morbidity and mortality. The immune response of young children differs in fundamental ways from that of adults, and these differences likely contribute to the increased susceptibility of children to severe malaria and to their delayed development of immunity. Elevated levels of pro-inflammatory cytokines and chemokines in the peripheral blood during acute infection contribute to the control of parasitaemia, but are also responsible for much of the immunopathology seen during symptomatic disease. Clinical immunity to malaria may depend upon the ability to regulate these pro-inflammatory responses, possibly through mechanisms of immunologic tolerance. In order to explore the effect of age on the immune response to malaria and the development of clinical immunity, cytokines and chemokines were measured in the plasma of children at day 0 of an acute malaria episode and during convalescence.ResultsYounger children presenting with acute malaria exhibited much higher levels of TNF, IL2, and IL6, as well as increased Th1 associated chemokines IP10, MIG, and MCP1, compared to older children with acute malaria. Additionally, the regulatory cytokines IL10 and TNFRI were dramatically elevated in younger children compared to older children during acute infection, indicating that regulatory as well as pro-inflammatory cytokine responses are dampened in later childhood.ConclusionsTogether these data suggest that there is a profound blunting of the cytokine and chemokine response to malaria among older children residing in endemic settings, which may be due to repeated malaria exposure, intrinsic age-based differences in the immune response, or both.

【 授权许可】

CC BY   
© The Author(s) 2017