Live Lactobacillus rhamnosus and Streptococcus pyogenes differentially regulate Toll‐like receptor (TLR) gene expression in human primary macrophages

Macrophages are phagocytes that rec- ognize bacteria and subsequently activate appro- priate innate and adaptive immune responses. TLRs are essential in identifying conserved bacte- rial structures and in initiating and mediating in- nate immune responses. In this work, we have characterized TLR gene expression in human monocyte-derived macrophages in response to stimulation with two live Gram-positive bacteria, a human commensal and probiotic Lactobacillus rhamnosus GG (LGG), and an important human pathogen Streptococcus pyogenes. LGG and S. pyogenes enhanced TLR2 expression in macro- phages. LGG and S. pyogenes also required TLR2 for NF-B activation. Only pathogenic S. pyogenes was able to up-regulate TLR3 and TLR7 gene ex- pression. This up-regulation was dependent on IFN-/, as neutralizing anti-IFN-/ antibodies reduced S. pyogenes-induced TLR3 and TLR7 mRNA expression. Our results show that despite similarities, TLR responses of macrophages differ for a Gram-positive probiotic and a pathogen. Our data suggest that macrophages can discriminate between probiotic and pathogenic bacteria by IFN- mediated TLR gene regulation. J. Leukoc. Biol. 84: 000-000; 2008.