Lactobacilli and streptococci induce inflammatory chemokine production in human macrophages that stimulates Th1 cell chemotaxis

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Abstract
Macrophages have a central role in innate‐immune responses to bacteria. In the present work, we show that infection of human macrophages with Gram‐positive pathogenic Streptococcus pyogenes or nonpathogenic Lactobacillus rhamnosus GG enhances mRNA expression of inflammatory chemokine ligands CCL2/monocyte chemoattractant protein‐1 (MCP‐1), CCL3/macrophage‐inflammatory protein‐1α (MIP‐1α), CCL5/regulated on activation, normal T expressed and secreted, CCL7/MCP‐3, CCL19/MIP‐3β, and CCL20/MIP‐3α and CXC chemokine ligands CXCL8/interleukin (IL)‐8, CXCL9/monokine induced by interferon‐γ (IFN‐γ), and CXCL10/IFN‐inducible protein 10. Bacteria‐induced CCL2, CCL7, CXCL9, and CXCL10 mRNA expression was partially dependent on ongoing protein synthesis. The expression of these chemokines and of CCL19 was dependent on bacteria‐induced IFN‐α/β production. CCL19 and CCL20 mRNA expression was up‐regulated by IL‐1β or tumor necrosis factor α (TNF‐α), and in addition, IFN‐α together with TNF‐α further enhanced CCL19 gene expression. Synergy between IFN‐α and TNF‐α was also seen for CXCL9 and CXCL10 mRNA expression. Bacteria‐stimulated macrophage supernatants induced the migration of T helper cell type 1 (Th1) cells, suggesting that in human macrophages, these bacteria can stimulate efficient inflammatory chemokine gene expression including those that recruit Th1 cells to the site of inflammation. Furthermore, L. rhamnosus‐induced Th1 chemokine production could in part explain the proposed antiallergenic properties of this bacterium.
Funding Information
  • Medical Research Council of the Academy of Finland
  • Finnish cancer foundation
  • Sigrid Juselius Foundation
  • Maud Kuistila Foundation