Activation of Human Monocytes by Live Borrelia burgdorferi Generates TLR2-Dependent and -Independent Responses Which Include Induction of IFN-β

• DOI: 10.1371/journal.ppat.1000444
• Publication Date: 2009-05-21T21:57:21Z
• Authors: Juan C. Salazar; Star Duhnam-Ems; Carson La Vake; Adriana R. Cruz; Meagan W. Moore; Melissa J. Caimano; Leonor Velez-Climent; Jonathan Shupe; Winfried Krueger; Justin D. Radolf
• Keywords: Proinflammatory cytokine; Monocyte

It is widely believed that innate immune responses to Borrelia burgdorferi (Bb) are primarily triggered by the spirochete's outer membrane lipoproteins signaling through cell surface TLR1/2. We recently challenged this notion demonstrating phagocytosis of live Bb peripheral blood mononuclear cells (PBMCs) elicited greater production proinflammatory cytokines than did equivalent bacterial lysates. Using whole genome microarrays, we show herein that, compared lysates, spirochetes a more intense and much broader transcriptional response involving genes associated with diverse cellular processes; among these were IFN-β number interferon-stimulated (ISGs), which not known result from TLR2 signaling. isolated monocytes, demonstrated activation signals interactions uptake degradation organisms within phagosomes. As PBCMs, induced markedly transcription secretion TNF-α, IL-6, IL-10 IL-1β in monocytes Secreted IL-18, which, like IL-1β, also requires cleavage activated caspase-1, was generated only Bb. Pro-inflammatory cytokine TLR2-deficient murine macrophages moderately diminished but drastically impaired against lysates; deficiency had no significant effect on spirochetes. PBMCs, potent inducer ISGs lysates or synthetic agonist. Collectively, our results indicate enhanced following have both TLR2-dependent -independent components latter induce type I IFNs ISGs.