Innate Immune Activation and Circulating Inflammatory Markers in Preschool Children.

Fiona Collier,Martin O’Hely,Siroon Bekkering,Mimi L K Tang,Cerys Chau,Keshav Faye-Chauhan,David Burgner,Toby Mansell,Peter Vuillermin,John Carlin,Richard Saffery,Lawrence E K Gray,Anne-Louise Ponsonby

doi:10.3389/fimmu.2021.830049

Abstract

Early childhood is characterised by repeated infectious exposures that result in inflammatory responses by the innate immune system. In addition, this inflammatory response to infection is thought to contribute to the epidemiological evidence linking childhood infection and adult non-communicable diseases. Consequently, the relationship between innate immune responses and inflammation during early life may inform prevention of NCDs later in life. In adults, non-genetic host factors such as age, sex, and obesity, strongly impact cytokine production and circulating mediators, but data in children are lacking. Here, we assessed cytokine responses and inflammatory markers in a population of healthy preschool children (mean age 4.2 years). We studied associations between cytokines, plasma inflammatory markers and non-genetic host factors, such as sex, age, adiposity, season, and immune cell composition. Similar to adults, boys had a higher inflammatory response than girls, with IL-12p70 and IL-10 upregulated following TLR stimulation. Adiposity and winter season were associated with increased circulating inflammatory markers but not cytokine production. The inflammatory markers GlycA and hsCRP were positively associated with production of a number of cytokines and may therefore reflect innate immune function and inflammatory potential. This dataset will be informative for future prospective studies relating immune parameters to preclinical childhood NCD phenotypes.

Highlights

Non-communicable diseases (NCDs) result in huge and increasing human and economic costs globally
We have presented the most important baseline characteristics for this study in Supplementary Table 1 according to sex. 285 participants were included in this study, with 52% male
But not granulocytes, were modestly higher in boys whereas the proportion of activated nonclassical monocytes in boys was lower (median 5.4 (IQR 3.4-8.1)% compared to 6.5 (4.2-10.2)%). high sensitivity C-reactive protein (hsCRP) levels were overall lower in males, 9 (6.1%) boys and 3 (2.1%) girls had hsCRP levels above 5ug/ml possibly indicative of active infection

Summary

Introduction

Non-communicable diseases (NCDs) result in huge and increasing human and economic costs globally. Development of innovative and effective prevention of NCDs requires better understanding of modifiable pathogenic pathways across the life course [1]. NCDs generally manifest in adulthood and disproportionately affect males [2, 3]. Innate Immunity in Young Children as a range of conditions and inflammation is the central pathogenic process [4]. The trajectories that lead to chronic inflammation begin in early life [5]. Understanding the variation and early determinants of inflammatory responses in healthy children may highlight opportunities for NCD prevention

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