Immunogenic molecules associated with gut bacterial cell walls: chemical structures, immune-modulating functions, and mechanisms

Interactions between gut microbiome and host immune system are fundamental to maintaining the intestinal mucosal barrier and homeostasis. At the host-gut microbiome interface, cell wall-derived molecules from gut commensal bacteria have been reported to play a pivotal role in training and remodeling host immune responses. In this article, we review gut bacterial cell wall-derived molecules with characterized chemical structures, including peptidoglycan and lipid-related molecules that impact host health and disease processes via regulating innate and adaptive immunity. Also, we aim to discuss the structures, immune responses, and underlying mechanisms of these immunogenic molecules. Based on current advances, we propose cell wall-derived components as important sources of medicinal agents for the treatment of infection and immune diseases.

Effects of deleting peptidoglycan hydrolase genes on the viable cell counts of Bacillus amyloliquefaciens and the yield of alkaline protease / 生物工程学报

In order to explore the effect of peptidoglycan hydrolase on the viable cell counts of Bacillus amyloliquefaciens and the yield of alkaline protease, five peptidoglycan hydrolase genes (lytC, lytD, lytE, lytF and lytG) of B. amyloliquefaciens TCCC111018 were knocked out individually. The viable cell counts of the bacteria and their alkaline protease activities before and after gene deletion were determined. The viable cell counts of the knockout mutants BA ΔlytC and BA ΔlytE achieved 1.67×106 CFU/mL and 1.44×106 CFU/mL respectively after cultivation for 60 h, which were 32.5% and 14.3% higher than that of the control strain BA Δupp. Their alkaline protease activities reached 20 264 U/mL and 17 265 U/mL, respectively, which were 43.1% and 27.3% higher than that of the control strain. The results showed that deleting some of the peptidoglycan hydrolase genes effectively maintained the viable cell counts of bacteria and increased the activity of extracellular enzymes, which may provide a new idea for optimization of the microbial host for production of industrial enzymes.

Effect of isotretinoin on peptidoglycan-induced expression of inflammatory genes in human SZ95 sebocytes / 中华皮肤科杂志

Objective To evaluate the effect of isotretinoin on expression of ache-associated inflammatory genes induced by peptidoglycan in human SZ95 sebocytes,and to explore the molecular mechanism underlying the treatment of acne with isotretinoin.Methods Cultured SZ95 sebocytes were divided into 3 groups:control group receiving no treatment,peptidoglycan group treated with 20 mg/L peptidoglycan alone,and costimulation group treated with 20 mg/L peptidoglycan combined with 10-5 mol/L isotretinoin.After 3-hour treatment,real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of pro-inflammatory cytokines including interleukin (IL)-1α,IL-1β,IL-6,IL-8,tumor necrosis factor (TNF)-α,Toll-like receptor 2 (TLR2) and MyD88 (a downstream gene of TLR2) in SZ95 sebocytes in the above groups.After 24-hour treatment,enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of IL-1α,IL-1β,IL-6,IL-8 and TNF-α in the cell culture supernatant in the above groups.After 48-hour treatment,Western blot analysis was conducted to determine the protein expression of TLR2 and MyD88.Statistical analysis was carried out with SPSS 23 software by one-way analysis of variance (ANOVA) for the comparison among the 3 groups,and by Bonferroni method for multiple comparisons.Results The mRNA and protein expression of pro-inflammatory cytokines including IL-1α,IL-1β,IL-6,IL-8 and TNF-α all significantly differed among the 3 groups (all P ＜ 0.01),and was significantly higher in the peptidoglycan group than in the control group and costimulation group (both P ＜ 0.016 7).The mRNA expression of MyD88 also significantly differed among the control group,peptidoglycan group and costimulation group (6.707 ± 0.950,10.270 ± 0.477,7.892 ± 0.900 respectively,F =10.17,P ＜ 0.01),and was significantly higher in the peptidoglycan group than in the control group and costimulation group (t =4.740,3.298 respectively,both P ＜ 0.016 7).The mRNA and protein expression of TLR2 were markedly higher in the peptidoglycan group than in the control group,but did not differ between the peptidoglycan group and the costimulation group.Conclusion Isotretinoin can inhibit peptidoglycan-induced expression of inflammatory factors possibly associated with the occurrence of acne in human SZ95 sebocytes,likely by inhibiting the expression of MyD88,but not TLR2,in the innate immune response,which may be one of the mechanisms underlying the treatment of acne with isotretinoin.

Characterization of the ligand binding of PGRP-L in half-smooth tongue sole (Cynoglossus semilaevis) by molecular dynamics and free energy calculation

Background: Peptidoglycan (PGN) recognition proteins (PGRPs) are important pattern recognition receptors of the host innate immune system that are involved in the immune defense against bacterial pathogens. PGRPs have been characterized in several fish species. The PGN-binding ability is important for the function of PGRPs. However, the PGRP-PGN interaction mechanism in fish remains unclear. In the present study, the 3-D model of a long PGRP of half-smooth tongue sole (Cynoglossus semilaevis) (csPGRP-L), a marine teleost with great economic value, was constructed through the comparative modeling method, and the key amino acids involved in the interaction with Lys-type PGNs and Dap-type PGNs were analyzed by molecular dynamics and molecular docking methods. Results: csPGRP-L possessed a typical PGRP structure, consisting of five ß-sheets and four α-helices. Molecular docking showed that the van der Waals forces had a slightly larger contribution than Coulombic interaction in the csPGRP-L-PGN complex. Moreover, the binding energies of csPGRP-L-PGNs computed by MM-PBSA method revealed that csPGRP-L might selectively bind both types of MTP-PGNs and MPP-PGNs. In addition, the binding energy of each residue of csPGRP-L was also calculated, revealing that the residues involved in the interaction with Lys-type PGNs were different from that with Dap-type PGNs. Conclusions: The 3-D structure of csPGRP-L possessed typical PGRP structure and might selectively bind both types of MTP- and MPP-PGNs, which provided useful insights to understanding the functions of fish PGRPs.

Nucleotide-binding oligomerization domain 1 is dispensable for host immune responses against pulmonary infection of Acinetobacter baumannii in mice / 한국실험동물학회지

Nucleotide-binding domain 1 (Nod1) is a cytosolic receptor that is responsible for the recognition of a bacterial peptidoglycan motif containing meso-diaminophimelic acid. In this study, we sought to identify the role of Nod1 in host defense in vivo against pulmonary infection by multidrug resistant Acinetobacter baumannii. Wildtype (WT) and Nod1-deficient mice were intranasally infected with 3×107 CFU of A. baumannii and sacrificed at 1 and 3 days post-infection (dpi). Bacterial CFUs, cytokines production, histopathology, and mouse β-defensins (mBD) in the lungs of infected mice were evaluated. The production of cytokines in response to A. baumannii was also measured in WT and Nod1-deficient macrophages. The bacterial clearance in the lungs was not affected by Nod1 deficiency. Levels of IL-6, TNF-α, and IL-1β in the lung homogenates were comparable at days 1 and 3 between WT and Nod1-deficient mice, except the TNF-α level at day 3, which was higher in Nod1-deficient mice. There was no significant difference in lung pathology and expression of mBDs (mBD1, 2, 3, and 4) between WT and Nod1-deficient mice infected with A. baumannii. The production of IL-6, TNF-α, and NO by macrophages in response to A. baumannii was also comparable in WT and Nod1-deficient mice. Our results indicated that Nod1 does not play an important role in host immune responses against A. baumannii infection.

Role of Rac1 signaling pathway of azathioprine and peptidoglycan in the regulation of monocyte-macrophage apoptosis in Crohn's disease / 中华内科杂志

Objective To evaluate the changes of macrophages and expression of Rac1 in the inflammatory site of Crohn's disease,and to investigate the effects of 6-thioguanine (6-TG) and peptidoglycan on apoptosis of human peripheral blood monocyte-macrophage by regulating Rac1 signaling pathway.Methods Ten patients with Crohn's disease and eight healthy controls diagnosed were enrolled at Department of Gastroenterology and Hepatology,Tianjin Medical University General Hospital from January 2013 to January 2014.The number of macrophages,apoptosis and expression of Rac1 in the inflammation sites and non-inflammation sites of intestinal mucosa were detected in both patients and controls.Peripheral blood mononuclear cells (PBMCs) were sorted by CD14 immunomagnetic beads.The apoptosis of monocytes,expression of Rac1 and related apoptosis signaling molecules were detected in patients treated with peptidoglycan,6-TG and Rac1 inhibitor NSC23766 and another 15 healthy donors.Results The number of macrophages and apoptotic cells significantly increased in the inflammatory group of Crohn's disease patients compared with the non-inflammatory group.The expression of PAK1,downstream molecular of Rac1 signaling pathway of macrophages was also significantly higher in the inflammatory group of Crohn's disease patients than that in healthy controls and non-inflammatory group.Compared with control group,anti-apoptotic signals (NF-κB,Bcl-xL and STAT-3) in PBMCs increased in the peptidoglycan group,while slightly decreased in 6-TG group.6-TG and NSC23766 significantly promoted peptidoglycan-related anti-apoptosis [peptidoglycan group (8.6±3.7)％,peptidoglycan + 6-TG group (42.0±2.7)％,peptidoglycan + NSC23766 group (58.5±6.9)％,P＜0.05].Conclusions Peptidoglycan plays a role in the pathogenesis of Crohn's disease by recruiting macrophages.However,6-TG inhibits peptidoglycan-induced activation of Rac 1 signaling pathway leading to macrophage apoptosis.

Expression of Toll-like Receptors, Pro-, and Anti-inflammatory Cytokines in Relation to Gut Microbiota in Irritable Bowel Syndrome: The Evidence for Its Micro-organic Basis

BACKGROUND/AIMS: A Subset of patients with irritable bowel syndrome (IBS) may have mild inflammation due to immune activation. Toll-like receptors (TLRs) and cytokines may cause intestinal inflammation. We studied their expression in relation to gut microbiota. METHODS: Expression of TLRs and cytokines was assessed in 47 IBS patients (Rome III) and 25 controls using quantitative real-time polymerase chain reaction. Immunohistochemistry was further performed to confirm the expression of TLR-4 and TLR-5. RESULTS: Of 47 patients with IBS, 20 had constipation (IBS-C), 20 diarrhea (IBS-D), and 7 unclassified (IBS-U). The mRNA levels of TLR-4 and TLR-5 were up-regulated in IBS patients than controls (P = 0.013 and P < 0.001, respectively). Expression of TLR-4 and TLR-5 at protein level was 4.2-folds and 6.6-folds higher in IBS-D than controls. The mRNA levels of IL-6 (P = 0.003), C-X-C motif chemokine ligand 11 (CXCL-11) (P < 0.001) and C-X-C motif chemokine receptor 3 (CXCR-3) (P < 0.001) were higher among IBS patients than controls. Expression of IL-6 (P = 0.002), CXCL-11 (P < 0.001), and CXCR-3 (P < 0.001) were up-regulated and IL-10 (P = 0.012) was down-regulated in IBS-D patients than controls. Positive correlation was seen between TLR-4 and IL-6 (P = 0.043), CXCR-3, and CXCL-11 (P = 0.047), and IL-6 and CXCR-3 (P = 0.003). Stool frequency per week showed positive correlation with mRNA levels of TLR-4 (P = 0.016) and CXCR-3 (P = 0.005), but inversely correlated with IL-10 (P = 0.002). Copy number of Lactobacillus (P = 0.045) and Bifidobacterium (P = 0.011) showed correlation with IL-10 in IBS-C, while Gram-positive (P = 0.031) and Gram-negative bacteria (P = 0.010) showed correlation with CXCL-11 in IBS-D patients. CONCLUSIONS: Altered immune activation in response to dysbiotic microbiota may promote intestinal inflammation in a subset of patients with IBS.

Peptidoglycan recycling and bacterial resistance to β-lactams / 中国药学杂志

To introduce peptidoglycan recycling and the β-lactams resistance mechanisms of bacteria, so that some help would be supplied to corresponding scientific workers and university teachers. By searching literatures, combined with our own studies, the bactericidal mechanisms of β-lactams and the resistance mechanisms of bacteria to β-lactams were summarized. The bactericidal activity of β-lactams is resulted from the inhibition of cell wall biosynthesis through combination with penicillin binding proteins such as transpeptidase destruction of peptidoglycan balances between biosynthesis and hydrolysis. The drug resistance of bacteria is resulted from the induction of β-lactamase, expression of out-pumping proteins, increase of outmembrane permeability, and modification of antibiotic target proteins. The proteins related to peptidoglycan recycling, such as transpeptidase and glycosyltransferase, would be potential targets for screening new β-lactams. The proteins related to β-lactams resistance, such as β-lactamase, would be potential targets for screening adjuvant drugs of β-lactams.

The role of glutamate and peptidoglycan in nanotubes formation between adjacent bacteria / 中国人兽共患病学报

We investigated the formation mechanism and immediate constituents of nanotubes between adjacent bacteria,pre venting rapid increase of drug-resistant bacteria provide potential targets.We used scanning electron microscopy(SEM) to observe formation of nanotubes;glutamic was determined by surface desorption atmospheric pressure chemical ionization mass spectrometry(SDAPCI-MS)and peptidoglycan was determined by enzyme linked immunosorbent assay(ELISA) in the forma tion of nanotubes before and after.The results showed that Staphylococcus aureus and Escherichia coli consumed more glutamic after formation of nanotubes;at the same time,the concentration of peptidoglycan in nanotubes formation of S.aureus and E.coli increased significantly.This study illuminated the glutamic and peptidoglycanin role mechanism of nanotubes form.We found that peptidoglycan is constituents of nanotubes and glutamic is the main energy source for the formation of nanotubes.

Effects of peptidoglycan with different concentrations on TLR2 and TLR4 in corneal epithelial cells of mice / 眼科新进展

Objective To investigate the effects of peptidoglycan (PGN) with different concentrations on Toll-like receptor 2 (TLR2),Toll-like receptor 4 (TLR4) expression in corneal epithelial cells of mice.Methods Corneal epithelial cells of c57 mice were cultured in vitro.Cells were divided into blank control group and 10 mg · L-1 group,30 mg · L-1 gruop and 80 mg · L-1 group (treated by different concentration of PGN for 12 hours).In the meantime,the cells in 30 mg · L-1 group were cultured for different times(named 12 hours group,24 hours group,36 hours group).Expressions of TLR2 and TLR4 mRNA and protein in different group were measured by RT-PCR and flow cytometry.Results Compared with control group (1.00 ± 0.14,1.00 ± 0.01),the expression of TLR2,LR4 mRNA in 10 mg · L-1 group (4.35 ± 0.46,3.53 ± 0.50),30 mg · L-1 group (8.06 ±0.72,5.31 ±0.34),80 mg · L-1 group (2.93 ±0.46,2.23 ±0.04) were increased,the differences were statistically significant (all P ＜ 0.05).Compared with control group,the expression of TLR2,TLR4 protein in different concentration group and 12 hour group were increased,the differences were statistically significant (all P ＜ 0.05).Conclusion PGN can up-regulate both mRNA and protein expression of TLR2 and TLR4 in corneal epithelial cells of mice,suggest that TLR2 and TLR4 in the corneal epithelial cell can recognize some exogenous pathogen and regulate the inflammatory reaction,which are closely related to the occurrence and development of infectious keratitis.

Advances in the research of inhibitors of enzymes of bacterial peptidoglycan biosynthesis / 药学学报

In recent years, owing to the abuse of antibiotics, the widespread of resistant bacterial strains became a serious threat to public health. This status demands development of new antibacterial agents with novel mechanisms of action. The reason for the limited new antibacterials is the small number of effective therapeutic targets, which cannot meet the current needs for the multiple drug-resistant treatment. Screening for new targets is the key step in the development of novel antibacterial agents. Peptidoglycan is the main component of the cell wall of bacteria, which is essential for survival of pathogenic bacteria. Within the biochemical pathway for peptidoglycan biosynthes is the Murligases, described in this review as highly potential targets for the development of new classes of antibacterial agents. This review provides an in-depth insight into the recent developments in the field of inhibitors of the Mur enzymes (MurA-F). Moreover, the reasons for the lack of candidate inhibitors and the challenges to overcome the hurdles are also discussed.

Texiobactin, a Potent Killer of Antibiotic Resistant Pathogens

Antibiotic resistance is a major global concern that primarily affects public health. Texiobactin is a newly discovered antibiotic produces by soil microbes isolated from natural environment. Drug is active against Gram-positive bacteria as it inhibits biosynthesis of peptidoglycan. Infection of methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae in mice elicits a good response reduce bacterial load. Although extensive efforts have been made to discover new antibiotics but results are still not satisfactory to meet the demands of public health. Recently it has been shown that the discovery of texiobactin by iChip will be a great stone mile to discover more antibiotics.

EFFECT OF STAPHYLO CO CCAL PEPTID O GLYCAN ON OSTEO CL AST DIFFERENTIATION / 中国修复重建外科杂志

OBJECTIVE: To investigate the effect of Staphylococcal peptidoglycan (PGN-sa) on raw264.7 cells differentiating into osteoclasts.

Potentiating activity of luteolin on membrane permeabilizing agent and ATPase inhibitor against methicillin-resistant Staphylococcus aureus

OBJECTIVE@#To investigate the mechanism of antibacterial activity of luteolin (LUT) against methicillin-resistant Staphylococcus aureus (MRSA).@*METHODS@#The mechanism of anti-MRSA activity of LUT was analyzed by the viability assay in membrane permeabilizing agent, ATPase inhibitors, and peptidoglycan (PGN) derived from Staphylococcus aureus (S. aureus). Also, transmission electron microscopy was used to monitor survival characteristics and changes in S. aureus morphology.@*RESULTS@#Compared to the LUT alone, the optical density of suspensions treated with the combination of 125 μg/mL Tris and 250 μg/mL N,N'-dicyclohexylcarbodiimide were reduced to 60% and 46% of the control, respectively. PGN (15.6 μg/mL) gradually impeded the activity of LUT, and PGN (62.5 μg/mL) completely blocked the activity of LUT on S. aureus.@*CONCLUSIONS@#Increased susceptibility to LUT with the Tris-dicyclohexylcarbodiimide combinations is evident in all tested MRSA isolates. The results indicate LUT synergy in increasing cytoplasmic membrane permeability and inhibiting ATPase. S. aureus PGN directly blocks the antibacterial activity of LUT, suggesting the direct binding of LUT with PGN. These findings may be validated for the development of antibacterial agent for low MRSA resistance.

Potentiating activity of luteolin on membrane permeabilizing agent and ATPase inhibitor against methicillin-resistant Staphylococcus aureus

Objective: To investigate the mechanism of antibacterial activity of luteolin (LUT) against methicillin-resistant Staphylococcus aureus (MRSA). Methods: The mechanism of anti-MRSA activity of LUT was analyzed by the viability assay in membrane permeabilizing agent, ATPase inhibitors, and peptidoglycan (PGN) derived from Staphylococcus aureus (S. aureus). Also, transmission electron microscopy was used to monitor survival characteristics and changes in S. aureus morphology. Results: Compared to the LUT alone, the optical density of suspensions treated with the combination of 125 μg/mL Tris and 250 μg/mL N,N'-dicyclohexylcarbodiimide were reduced to 60% and 46% of the control, respectively. PGN (15.6 μg/mL) gradually impeded the activity of LUT, and PGN (62.5 μg/mL) completely blocked the activity of LUT on S. aureus. Conclusions: Increased susceptibility to LUT with the Tris-dicyclohexylcarbodiimide combinations is evident in all tested MRSA isolates. The results indicate LUT synergy in increasing cytoplasmic membrane permeability and inhibiting ATPase. S. aureus PGN directly blocks the antibacterial activity of LUT, suggesting the direct binding of LUT with PGN. These findings may be validated for the development of antibacterial agent for low MRSA resistance.

Structural insights into the regulatory mechanism of the Pseudomonas aeruginosa YfiBNR system

YfiBNR is a recently identified bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) signaling system in opportunistic pathogens. It is a key regulator of biofilm formation, which is correlated with prolonged persistence of infection and antibiotic drug resistance. In response to cell stress, YfiB in the outer membrane can sequester the periplasmic protein YfiR, releasing its inhibition of YfiN on the inner membrane and thus provoking the diguanylate cyclase activity of YfiN to induce c-di-GMP production. However, the detailed regulatory mechanism remains elusive. Here, we report the crystal structures of YfiB alone and of an active mutant YfiB(L43P) complexed with YfiR with 2:2 stoichiometry. Structural analyses revealed that in contrast to the compact conformation of the dimeric YfiB alone, YfiB(L43P) adopts a stretched conformation allowing activated YfiB to penetrate the peptidoglycan (PG) layer and access YfiR. YfiB(L43P) shows a more compact PG-binding pocket and much higher PG binding affinity than wild-type YfiB, suggesting a tight correlation between PG binding and YfiB activation. In addition, our crystallographic analyses revealed that YfiR binds Vitamin B6 (VB6) or L-Trp at a YfiB-binding site and that both VB6 and L-Trp are able to reduce YfiB(L43P)-induced biofilm formation. Based on the structural and biochemical data, we propose an updated regulatory model of the YfiBNR system.

Oleanolic acid and ursolic acid inhibit peptidoglycan biosynthesis in Streptococcus mutans UA159

In this study, we revealed that OA and UA significantly inhibited the expression of most genes related to peptidoglycan biosynthesis in S. mutans UA159. To the best of our knowledge, this is the first report to introduce the antimicrobial mechanism of OA and UA against S. mutans.

Peptidoglycan Up-Regulates CXCL8 Expression via Multiple Pathways in Monocytes/Macrophages

Peptidoglycan (PG), the gram positive bacterial pathogen-associated molecular patterns (PAMP), is detected in a high proportion in macrophage-rich atheromatous regions, and expression of chemokine CXCL8, which triggers monocyte arrest on early atherosclerotic endothelium, is elevated in monocytes/macrophages in human atherosclerotic lesion. The aim of this study was to investigate whether PG induced CXCL8 expression in the cell type and to determine cellular signaling pathways involved in that process. Exposure of THP-1 cell, human monocyte/macrophage cell line, to PG not only enhanced CXCL8 release but also profoundly induced il8 gene transcription. PG-induced release of CXCL8 and induction of il8 gene transcription were blocked by OxPAPC, an inhibitor of TLR-2/4 and TLR4, but not by polymyxin B, an inhibitor of LPS. PG-mediated CXCL8 release was significantly attenuated by inhibitors of PI3K-Akt-mTOR pathways. PKC inhibitors, MAPK inhibitors, and ROS quenchers also significantly attenuated expression of CXCL8. The present study proposes that PG contributes to inflammatory reaction and progression of atherosclerosis by inducing CXCL8 expression in monocytes/macrophages, and that TLR-2, PI3K-Akt-mTOR, PKC, ROS, and MAPK are actively involved in the process.

The role of mannan-binding lectin in inhibition of inflammatory responses induced by peptidoglycan and its mechanism in THP-1/CD14 cells / 中华微生物学和免疫学杂志

Objective To investigate the effects of mannan-binding lectin(MBL) on TNF-α production induced by peptidoglycan (PGN) and its mechanism in human THP-1/CD14 monocytes.Methods The THP-1/CD14 cells were stimulated for 24 h with PGN at the indicated ratios after pretreated with human natural MBL at concentrations ranging from 1 to 20 mg/L for 2 h.The content of TNF-α and IL-6 in culture supernatants were detected by ELISA,and the levels of TNF-α and IL-6 mRNA expressions in these cells were determined by RT-PCR.FACS was used to investigate the interaction of MBL with THP-1/CD14 cells and the impact of MBL on PGN binding to THP-1/CD14 cells.Western blot was used to detect PGN-induced NF-κB translocation in THP-1/CD14 cells.Results ELISA showed that secretion of TNF-α and IL-6 from THP-1/CD14 cells could be induced by PGN ;The productions of TNF-α and IL-6 by THP-1/CD14 cells induced with PGN were profoundly inhibited by MBL at higher concentrations (10-20 mg/L) but not MBL at lower concentrations (1 mg/L).RT-PCR analysis also indicated that the mRNA expressions of TNF-α and IL-6 in THP-1/CD14 cells were decreased by MBL at higher concentration,compared to the corresponding THP-1/CD14 cells stimulated with PGN only.FACS showed that the binding of MBL to THP-1/CD14 cells was evident in a Ca2+-dependent manner.PGN could competitively inhibit the binding of MBL to THP-1/CD14 cells.MBL could competitively inhibit the binding of PGN to THP-1/CD14 cells by binding to THP-1/CD14 cells directly.Similarly,MBL at higher concentration (20 mg/L) decreased the NF-κB translocation in THP-1/CD14 cells.Conclusion MBL may inhibit TNF-α and IL-6 production induced by PGN in THP-1/CD14 cells through NF-κB signaling pathways,suggesting that MBL can play some roles in the regulation of PGN-induced inflammatory response.

Peptidoglycan from Staphylococcus aureus induces the overexpression of TRLs 1-8 mRNA in corneal fibroblasts, but its lipoteichoic acid and muramyl dipeptide only induced the overexpression of TLR5 or TRL9

Lipopolysaccharide induces TLR-1-8 mRNAs over-expression in corneal fibroblast. Analyzing if other TLR-ligands can do the same, we found that peptidoglycan does, but not muramyldipeptide, lipoteichoic acid and polyI:C. This suggests that the recognition of lipopolysaccharide and peptidoglycan is enough to alert these cells against microorganisms through the over-expression of the majority TLRs.