Toll like receptor 2 agonists lipoteichoic acid and peptidoglycan are able to enhance antigen specific IFNγ release in whole blood during recall antigen responses

Dammermann, Werner; Wollenberg, Lisa; Bentzien, Frank; Lohse, Ansgar W.; Lüth, Stefan

doi:10.1016/j.jim.2013.08.004

Cited by 27 publications

(16 citation statements)

References 26 publications

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“…Pneumococcal LTA, the glycolipid anchor of which has unsaturated fatty acids, showed 100-fold less TLR stimulation than staphylococcal LTA consisting of only saturated fatty acids, as reported by Han et al (2003). Although LTA recognition by TLR2 is actually under debate (Dammermann et al 2013; Fischer et al 2011; Ray et al 2013; Schmidt et al 2011), it is plausible from our study that the relatively low immunomodulatory effect of B. cereus LTA could be partially linked to the nature of the acyl chains. On the other hand, the d -alanine substitution rate of B. cereus LTA is the highest from the three studied strains (41 %), while this LTA was the less immunostimulatory.…”

Section: Resultsmentioning

confidence: 68%

Characterization of lipoteichoic acid structures from three probiotic Bacillus strains: involvement of d-alanine in their biological activity

Villéger

Saad

Grenier

et al. 2014

Antonie van Leeuwenhoek

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Probiotics represent a potential strategy to influence the host’s immune system thereby modulating immune response. Lipoteichoic Acid (LTA) is a major immune-stimulating component of Gram-positive cell envelopes. This amphiphilic polymer, anchored in the cytoplasmic membrane by means of its glycolipid component, typically consists of a poly (glycerol-phosphate) chain with d-alanine and/or glycosyl substitutions. LTA is known to stimulate macrophages in vitro, leading to secretion of inflammatory mediators such as Nitric Oxide (NO). This study investigates the structure–activity relationship of purified LTA from three probiotic Bacillus strains (Bacillus cereus CH, Bacillus subtilis CU1 and Bacillus clausii O/C). LTAs were extracted from bacterial cultures and purified. Chemical modification by means of hydrolysis at pH 8.5 was performed to remove d-alanine. The molecular structure of native and modified LTAs was determined by 1H NMR and GC–MS, and their inflammatory potential investigated by measuring NO production by RAW 264.7 macrophages. Structural analysis revealed several differences between the newly characterized LTAs, mainly relating to their d-alanylation rates and poly (glycerol-phosphate) chain length. We observed induction of NO production by LTAs from B. subtilis and B. clausii, whereas weaker NO production was observed with B. cereus. LTA dealanylation abrogated NO production independently of the glycolipid component, suggesting that immunomodulatory potential depends on d-alanine substitutions. d-alanine may control the spatial configuration of LTAs and their recognition by cell receptors. Knowledge of molecular mechanisms behind the immunomodulatory abilities of probiotics is essential to optimize their use.

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Section: Resultsmentioning

confidence: 68%

Characterization of lipoteichoic acid structures from three probiotic Bacillus strains: involvement of d-alanine in their biological activity

Villéger

Saad

Grenier

et al. 2014

Antonie van Leeuwenhoek

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“…Gram-positive and anaerobic P. acnes have been implicated in acne inflammation and pathogenesis. LTA and PGN are the main components of P. acnes that trigger TLR2 activation and the release of the neutrophil chemoattractant cytokine IL-8 (16). On the other hand, LTA triggers TLR4 activation.…”

Section: Discussionmentioning

confidence: 99%

Establishment of an Anti-acne Vulgaris Evaluation Method Based on TLR2 and TLR4-mediated Interleukin-8 Production

Suvanprakorn¹,

Tongyen²,

Prakhongcheep

et al. 2019

In Vivo

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Background/Aim: To date, no cell-based assay that focuses on the prime cause of acne initiation through activation of toll-like receptor2 and 4 and interleukin-8 (IL-8) production exists. Herein, we present an assay that evaluates acne by determining TLR2 and 4 expression and activation. Materials and Methods: Viability of keratinocytes was determined by the MTT assay. IL-8 was evaluated by ELISA. Immunocytochemistry was performed for determining receptor expression. Results: Lipoteichoic acid (LTA), peptidoglycan (PGN) and lipopolysaccharide (LPS) induced IL-8 production. Pre-treatment of cells with TLR2 and TLR4 inhibitors, before stimulation, reduced IL-8 production. Zinc gluconate was used for verification. Zinc can significantly suppress IL-8 production in the system. Treatment of cells with LTA+PGN or LPS resulted in increased TLR2 and TLR4 expression on the cell surface. This effect was prevented by zinc treatment. Conclusion: The measurement of IL-8 and TLR2 and TLR4 levels can be used for the evaluation of anti-acne treatment. Acne vulgaris is a chronic disease. It is common among adolescents and can have a huge impact on physical appearance and health both short-term and long-term as a result of the adverse effects of the medication (1). The adverse effects are induced by non-anti-acne actions such as antibiotics and steroids (2). It is known that inflammation derived from the activation of innate immunity plays a primary role in the induction of acne lesions rather than infection or an allergic reaction (3). Clinically, there are multiple types of acne lesions. However, the induction of all types of lesions is primarily initiated by colonization of Propionibacterium acnes, a Gram-positive anaerobic bacterium that plays a key role in maintaining and influencing the inflammatory phase of acne (4). The major cell wall components of P. acnes, lipoteichoic acid (LTA) and peptidoglycan (PGN) were found to stimulate immune cells to release mediators of inflammation (5). Apart from LTA and PGN, lipopolysaccharide (LPS)-a component of gram-negative bacteria-is also an immunostimulatory factor (6). The innate immune system of the skin epidermis has several defense components and mechanisms involving keratinocytes, neutrophils, mast cells and macrophages (7). The key step of acne formation is the interaction of bacterial components such as LPS, LTA or PGN with toll-like receptors (TLRs) in epidermal cells (8). TLR4 primarily mediates cellular signaling induced by Gram-negative bacteria (9), while TLR2 is required for pro-inflammatory signaling to components of Gram-positive bacteria (10). It is known that TLR2 and TLR4 are predominantly expressed on the cell surface of the infundibular keratinocytes. The activation of these TLRs results in signaling cascades that produce interleukin 8 (IL-8) (11). As a consequence, IL-8 acts as a pro-inflammatory cytokine and a powerful chemoattractant (12). This cytokine plays a major role in inflammatory events by its activity as chemokine and as an activator of crucial neutrop...

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“…Families of TLRs and C-type lectin receptors are essential for macrophages to function normally. TLR2 and TLR4 are two receptors that participate in immunity against Mtb by mediating the secretion of proinflammatory cytokines [ 18 , 20 , 33 , 34 ]. Here, TLR2 and TLR4 expression on MDMs exposed to LAM were analyzed during differentiation and observation showed that when monocytes were exposed to LAM for 96 h, the frequency of TLR2 + macrophages was reduced compared to both monocytes and macrophages that had never been in contact with LAM ( Figure 6(b) ).…”

Section: Discussionmentioning

confidence: 99%

Exposure of Monocytes to Lipoarabinomannan Promotes Their Differentiation into Functionally and Phenotypically Immature Macrophages

Chávez‐Galán¹,

Ocaña-Guzmán²,

Torre-Bouscoulet³

et al. 2015

Journal of Immunology Research

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Lipoarabinomannan (LAM) is a lipid virulence factor secreted by Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis. LAM can be measured in the urine or serum of tuberculosis patients (TB-patients). Circulating monocytes are the precursor cells of alveolar macrophages and might be exposed to LAM in patients with active TB. We speculated that exposing monocytes to LAM could produce phenotypically and functionally immature macrophages. To test our hypothesis, human monocytes were stimulated with LAM (24–120 hours) and various readouts were measured. The study showed that when monocytes were exposed to LAM, the frequency of CD68+, CD33+, and CD86+ macrophages decreased, suggesting that monocyte differentiation into mature macrophages was affected. Regarding functionality markers, TLR2+ and TLR4+ macrophages also decreased, but the percentage of MMR+ expression did not change. LAM-exposed monocytes generated macrophages that were less efficient in producing proinflammatory cytokines such as TNF-α and IFN-γ; however, their phagocytic capacity was not modified. Taken together, these data indicate that LAM exposure influenced monocyte differentiation and produced poorly functional macrophages with a different phenotype. These results may help us understand how mycobacteria can limit the quality of the innate and adaptive immune responses.

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Toll like receptor 2 agonists lipoteichoic acid and peptidoglycan are able to enhance antigen specific IFNγ release in whole blood during recall antigen responses

Cited by 27 publications

References 26 publications

Characterization of lipoteichoic acid structures from three probiotic Bacillus strains: involvement of d-alanine in their biological activity

Characterization of lipoteichoic acid structures from three probiotic Bacillus strains: involvement of d-alanine in their biological activity

Establishment of an Anti-acne Vulgaris Evaluation Method Based on TLR2 and TLR4-mediated Interleukin-8 Production

Exposure of Monocytes to Lipoarabinomannan Promotes Their Differentiation into Functionally and Phenotypically Immature Macrophages

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