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- Title
Gram-Positive and Gram-Negative Bacteria Synergize with Oxidants to Release CXCL8 from Innate Immune Cells.
- Authors
Paul-Clark, Mark J.; Sorrentino, Rosalinda; Bailey, Lucy K.; Sriskandan, Shiranee; Mitchell, Jane A.
- Abstract
We have recently demonstrated that oxidants can activate monocytes via an action on Toll-like receptor (TLR) 2; however, it is unclear what functional consequence this has on immune surveillance for Gram-negative and -positive bacteria. Gramnegative and -positive bacteria and their related pathogen-associated molecular patterns (PAMPs) are sensed by TLR4 and TLR2, respectively. In the current study, we used a human monocyte cell line to show that oxidants prime cells to subsequent challenge with Gram-negative or -positive bacteria as well as PAMPs specific for TLR4 (LPS), TLR2/1 (Pam3CSK4), TLR2/6 (FSL-1), Nod1 (FK565), and Nod2 (MDP Lys 18). Similarly, activation of TLR4 with LPS primed for subsequent activation of cells by agonists of the TLR2/6 or TLR2/1 complex. However, no synergy was noted when cells were costimulated with Pam3CSK4 and FSL-1. We then tested blood (and isolated monocytes) derived from healthy smokers, which is oxidant primed, making it more sensitive to bacterial or PAMP stimulation when compared with blood of nonsmokers. Thus an oxidant stimulation, possibly via an action on TLR2 or associated transduction pathways, provides a signal that initiates inflammatory responses and sensitizes cells to pathogenic insults.
- Subjects
BACTERIA; MONOCYTES; PATHOGENIC microorganisms; OXIDIZING agents; NATURAL immunity; CHEMICAL agonists
- Publication
Molecular Medicine, 2008, Vol 14, Issue 5/6, p238
- ISSN
1076-1551
- Publication type
Article
- DOI
10.2119/2007-00098.Paul-Clark