Maturation of Toll-like receptor 1-4 responsiveness during early life

Toll-like receptors (TLRs) are part of the highly conserved components of the innate immune system, and have been investigated extensively; however, little is known about TLR function during early postnatal life, a critical period for immune maturation.

In order to achieve a more complete understanding of the ontogeny of immune system during the first years of life, our study investigated age-matched TLR1-4 responsiveness at several time points up to the age of two years.

Mononuclear cells were isolated from cord blood (n=150) and peripheral blood from infants at 6 (n=68), 12 (n=75), and 24 (n=74)months of age, and from 50 adults. Cells were stimulated with Toll-like receptor ligands (TLR1-4) and phytohemagglutinin (PHA). Stimulated cells were assessed for their production of the cytokines tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), and for TLR4 gene expression.

Our results suggested that cord response of IL-6 and TNF-α was not affected by allergic background. In addition, neonatal mononuclear cell had enhanced IL-6 production upon TLR1, 2, and 4 stimulations as compared to those of young children and adults. Nevertheless, after 6 months of age, the level remained comparable throughout the first two years of life. While TNF-α response to all TLR stimulations remained fairly similar during early life. This cytokine pattern closely paralleled our findings for TLR4 mRNA expression, and longitudinal cytokine changes within the same individual.

Our findings provided additional information to the understanding of immune development during early life, and offered stronger evidence of neonatal innate immunity being capable of responding adequately to TLR stimulation.