Malarial Cytokine Responses Reduced by Age in Exposed Children

Elevated levels of pro-inflammatory cytokines and chemokines in the peripheral blood during acute malaria infection contribute to the control of parasitemia, but are also responsible for much of the immunopathology seen during symptomatic disease.

Young 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.

An international team of scientists working with those at University of California San Francisco (CA, USA) obtained blood samples from study cohort that was initiated in 2011 and is ongoing. This cohort consists of 100 households where malaria transmission in this region is holoendemic, with an annual entomological inoculation rate (EIR) of 310 infective bites per person year. In total, plasma samples from 48 children were analyzed: 25 from children 1 to 3 years old and 23 from children 7 to 10 years old.

Thick blood smears were stained with 2% Giemsa for 30 minutes. Thick smears were evaluated for the presence of parasitemia (asexual forms only) and gametocytes. The concentrations of 20 cytokines and chemokines were measured in plasma samples using Luminex technology. Fourteen cytokines and six chemokines were analyzed using a custom R&D Magnetic Luminex Screening Assay Human Premixed Multi-Analyte Kit and read on a Luminex MAGPIX CCD Imager. Human interferon gamma (IFNγ) OptEIA ELISA II Kits were used to quantify IFNγ levels in plasma.

The team found that younger children presenting with acute malaria exhibited much higher levels of tumor necrosis factor (TNF), interleukin-2 (IL2), and IL6, as well as increased T helper cells (Th1) associated chemokines interferon gamma-induced protein 10 (IP10), Monokine induced by gamma interferon (MIG), and monocyte chemoattractant protein-1 (MCP1), was compared to older children with acute malaria. Additionally, the regulatory cytokines IL10 and tumor necrosis factor receptor 1 (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.

The authors concluded that that despite age-related differences in immune responses, young children respond with a largely pro-inflammatory Th1-type cytokine and chemokine response, similar to naïve travelers; however, they also show increased levels of the regulatory cytokines IL10 and soluble TNFRI, which may limit their ability to develop robust immunity to subsequent malaria infections. The study was published on December 29, 2017, in the Malaria Journal.

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