Pre- and postnatal administration of Lactobacillus reuteri decreases TLR2 responses in infants

Anna Forsberg, Thomas R Abrahamsson, Bengt Björkstén, Maria C Jenmalm, Anna Forsberg, Thomas R Abrahamsson, Bengt Björkstén, Maria C Jenmalm

Abstract

Background: Mice models indicate that intact Toll like receptor (TLR) signaling may be essential for the allergy protective effects of diverse bacterial exposure observed in clinical trials and epidemiological studies. Probiotic supplementation with Lactobacillus reuteri from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE-associated eczema at two years (ClinicalTrials.gov NCT01285830). The effect of this supplementation on innate immune responses to bacterial products and the expression of associated TLRs were explored.

Methods: Blood mononuclear cells were collected at birth, 6, 12 and 24 months from 61 infants and cultured with TLR2, 4 and 9 ligands. Cytokine and chemokine secretion was determined as well as TLR2, 4 and 9 mRNA expression.

Results: Probiotic supplementation was associated with decreased LTA (lipoteichoic acid) induced CCL4, CXCL8, IL-1β and IL-6 responses at 12 months and decreased CCL4 and IL-1β secretion at 24 months. TLR2 mRNA expression was not affected by probiotic treatment.

Conclusions: Decreased responses to TLR2, the main receptor for LTA from Gram positive bacteria, in probiotic treated children seem to be dependent on factors downstream of TLR mRNA expression.

Keywords: Allergy; Chemokine; Cytokine; Eczema; Infancy; Lactobacillus reuteri; Probiotics; Sensitization; TLR.

Figures

Figure 1
Figure 1
LTA induced responses. LTA induced IL-1β (A), IL-6 (B), CCL4 (C), CXCL8 (D), responses from peripheral blood mononuclear cells during the two first years in life in probiotic (filled squares) and placebo (open circles) treated children. Groups were compared using Mann–Whitney U-test, **p < 0.01, *p < 0.05. The number of analyzed samples is indicated (n), as well as the median values.
Figure 2
Figure 2
TLR4 mRNA expression. Comparison of TLR4 mRNA expression of peripheral blood mononuclear cells during the two first years in life in probiotic (filled squares) and placebo (open circles) treated children. The values represent TLR4/18S expression ratios. Groups were compared using Mann–Whitney U-test, *p < 0.05. The number of analysed samples is indicated (n), as well as the median values.
Figure 3
Figure 3
TLR2 mRNA expression. Comparison of TLR2 mRNA expression of peripheral blood mononuclear cells during the two first years in life in non-allergic (open triangles) and allergic children (filled circles). The values represent TLR2/18S expression ratios. Groups were compared using Mann–Whitney U-test, *p < 0.05. The number of analysed samples is indicated (n), as well as the median values.

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Source: PubMed

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