TLR-independent induction of human monocyte IL-1 by phosphoglycolipids from thermophilic bacteria

Abstract

The structures of phosphoglycolipids PGL1 and PGL2 from the thermophilic bacteria Meiothermus taiwanensis, Meiothermus ruber, Thermus thermophilus, and Thermus oshimai are determined recently (Yang et al. in J Lipid Res. 47:1823-1932, 2006). These bacteria belong to Gram-negative bacteria that do not contain lipopolysaccharide, but high amounts of phosphoglycolipids and glycoglycerolipids. Here we show that PGL1/PGL2 mixture (PGL1: PGL2 = 10:1 ~ 10:2) from M. taiwanensis and T. oshimai, but not T. thermophilus and M. ruber, up-regulate interleukin-1beta (IL-1beta) production in human THP-1 monocytes and blood-isolated primary monocytes. PGL2 was purified after phospholipase A2 hydrolysis of PGL1 in the PGL1/PGL2 mixture followed by column chromatography. PGL2 did not induce proIL-1 production, even, partially (35-40%) inhibited PGL1-mediated proIL-1 production, showing that PGL1 is the main inducer of proIL-1 production in PGL1/PGL2 mixture. The production of proIL-1 stimulated by phosphoglycolipids was strongly inhibited by specific PKC-alpha, MEK1/2, and JNK inhibitors, but not by p38-specific inhibitor. The intracellular calcium influx was involved in phosphoglycolipids-mediated proIL-1 production. Using blocking antibody and Toll-like receptor (TLR)-linked NF-kappaB luciferase assays, we found that the cellular receptor(s) for phosphoglycolipids on proIL-1 production was TLR-independent. Further, phosphoglycolipids isolated from T. thermophilus and M. ruber did not induce proIL-1 production, even though T. thermophilus possess more PGL1 than PGL2 (6:4). Specially, the fatty acid composition of phosphoglycolipids from both T. thermophilus and M. ruber consists of a low percentage of C15 (<10%) and a high percentage of C17 (>75%). It suggests, the C15 percentage of PGL may play a critical role in PGL-mediated proIL-1 induction.

TLR2, TLR4 and CD14 Recognize Venom-Associated Molecular Patterns from Tityus serrulatus to Induce Macrophage-Derived Inflammatory Mediators

“…TLR2 cooperates with TLR6 in response to diacylated mycoplasma lipopeptide [60] and associates with TLR1 to recognize triacylated lipopeptides [61]. It has been well established that TLRs can recognize infectious agents by sensing PAMPs and triggering the antimicrobial immune responses of the host [62], [63]; however, emerging evidence indicates that certain molecules can also activate TLRs, such as TLR2-MyD88, independent of TLR1 and TLR6 [64]. We observed that the activation of NF-κB occurred in a MyD88-dependent manner as a result of TLR2 and TLR4 stimulation, suggesting that these receptors are important in the response to TsV.…”

Immunostimulatory Phosphatidylmonogalactosyldiacylglycerols (PGDG) from the Marine Diatom Thalassiosira weissflogii: Inspiration for a Novel Synthetic Toll-Like Receptor 4 Agonist

“…Among these lipids, bacterial lipopolysaccharide (LPS) and its synthetic derivative monophosphoryl lipid A (MPLA) are the most widely studied agonists of TLR-4 [42]. Glycerol-based lipids with phosphate and carbohydrate in their structure represent another group of lipids for which an immunomodulant activity has been analyzed, even though only in a limited number of cases [13,15,43,44]. The best-known member of this group is lipotheicoic acid (LTA), composed by a glycoglycerolipid bound to a hydrophilic polymer of glycerophosphate, for which a specific TLR-2 agonistic activity has been documented [13,44].…”

Ehrlichia chaffeensis Induces Monocyte Inflammatory Responses through MyD88, ERK, and NF-κB but Not through TRIF, Interleukin-1 Receptor 1 (IL-1R1)/IL-18R1, or Toll-Like Receptors

“…VP1680, a T3SS effector protein of Vibrio parahaemolyticus, is responsible for IL-8 induction in Caco-2 cells, which is mediated by activation of both the ERK signaling pathway and NF-B (44). Phosphoglycolipids from thermophilic bacteria such as Meiothermus taiwanensis induce IL-1 in human monocytes through a mechanism involving PKC-␣, MEK1/2, and JNK, but independently of TLRs (53). In all of these cases, cytokine induction is inde- , and freeze-thawed Wakulla induces strong proinflammatory cytokine induction (data not shown), bacterial infection does not seem to be required for this early response.…”