Expression and function of toll-like receptor 2 in vertebrate

Pergolizzi, Simona; Fumia, Angelo; D’Angelo, Roberta; Mangano, Angelica; Lombardo, Giorgia Pia; Giliberti, Angelo; Messina, Emmanuele; Alesci, Alessio; Lauriano, Eugenia Rita

doi:10.1016/j.acthis.2023.152028

Cited by 8 publications

(8 citation statements)

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“…Zymosan-induced paw inflammation is often used to study TLR2-mediated innate immune responses directed against Gram-positive bacteria, fungi, viruses, protozoa and helminths. TLR2 is nearly ubiquitously expressed and has been reported, for example, for keratinocytes, fibroblasts, neurons and nearly all immune cells (Flo et al, 2001;Goethals et al, 2010;Pergolizzi et al, 2023). Activation of TLR2 by zymosan induces the expression of various PI proteins, including COX-2, which is followed by increased prostanoid synthesis (i.e., PGE 2 ) (Bansal et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Meloxicam treatment disrupts the regional structure of innate inflammation sites by targeting the pro‐inflammatory effects of prostanoids

Schäufele,

Kolbinger,

Friedel

et al. 2023

British J Pharmacology

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Background and PurposeNon‐steroidal anti‐inflammatory drugs (NSAIDs) are the most widely prescribed drugs in the world due to their analgesic, antipyretic and anti‐inflammatory effects. However, NSAIDS inhibit prostanoid synthesis, interfering with their pro‐inflammatory and anti‐inflammatory functions, and potentially prolonging acute inflammation.Experimental ApproachWe used high‐content immunohistochemistry to define the impact of meloxicam treatment on spatially separated pro‐ and anti‐inflammatory processes during innate inflammation in mice induced by zymosan. This allowed us to determine the effect of meloxicam treatment on the organization of pro‐ and anti‐inflammatory microenvironments thereby identifying relevant changes in immune cell localization, recruitment and activation.Key ResultsMeloxicam treatment reduced zymosan‐induced thermal hypersensitivity at early time points but delayed its resolution. High‐content immunohistochemistry revealed that the pro‐inflammatory area was smaller after treatment, diminishing neutrophil recruitment, M1‐like macrophage polarization, and especially phagocytosis by neutrophils and macrophages. The polarization of macrophages toward the M2‐like anti‐inflammatory phenotype was unaffected and the number of anti‐inflammatory eosinophils actually increased.Conclusion and ImplicationsHigh‐content immunohistochemistry was able to identify relevant meloxicam‐mediated effects on inflammatory processes based on alterations in the regional structure of inflammation sites. Meloxicam delayed the clearance of pathogens by inhibiting pro‐inflammatory processes, causing prolonged inflammation. Our data suggest that the prescription of NSAIDs as a treatment during an acute pathogen‐driven inflammation should be reconsidered in patients with compromised immune systems.

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Section: Introductionmentioning

confidence: 99%

Meloxicam treatment disrupts the regional structure of innate inflammation sites by targeting the pro‐inflammatory effects of prostanoids

Schäufele,

Kolbinger,

Friedel

et al. 2023

British J Pharmacology

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“…Toll-like receptors (TLRs) are a class of phylogenetically highly conserved transmembrane proteins that play an important role in the innate immune system by recognizing pathogen-associated molecular patterns (PAMPs) and initiating immune responses [ 67 , 68 , 69 , 70 ]. We previously demonstrated TLR2 expression in the defense cells of invertebrates [ 71 , 72 ], protochordates [ 73 , 74 ], and several aquatic vertebrates such as myxins [ 74 , 75 ], cartilaginous fish [ 76 ], and bony fish [ 77 , 78 , 79 ].…”

Section: Discussionmentioning

confidence: 99%

Internal Defense System of Mytilus galloprovincialis (Lamarck, 1819): Ecological Role of Hemocytes as Biomarkers for Thiacloprid and Benzo[a]Pyrene Pollution

Alesci,

Di Paola,

Fumia

et al. 2023

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The introduction of pollutants, such as thiacloprid and benzo[a]pyrene (B[a]P), into the waters of urbanized coastal and estuarine areas through fossil fuel spills, domestic and industrial waste discharges, atmospheric inputs, and continental runoff poses a major threat to the fauna and flora of the aquatic environment and can have a significant impact on the internal defense system of invertebrates such as mussels. Using monoclonal and polyclonal anti-Toll-like receptor 2 (TLR2) and anti-inducible nitric oxide synthetase (iNOS) antibodies for the first time, this work aims to examine hemocytes in the mantle and gills of M. galloprovincialis as biomarkers of thiacloprid and B[a]P pollution and analyze their potential synergistic effect. To pursue this objective, samples were exposed to the pollutants, both individually and simultaneously. Subsequently, oxidative stress biomarkers were evaluated by enzymatic analysis, while tissue changes and the number of hemocytes in the different contaminated groups were assessed via histomorphological and immunohistochemical analyses. Our findings revealed that in comparison to a single exposure, the two pollutants together significantly elevated oxidative stress. Moreover, our data may potentially enhance knowledge on how TLR2 and iNOS work as part of the internal defense system of bivalves. This would help in creating new technologies and strategies, such as biosensors, that are more suitable for managing water pollution, and garnering new details on the condition of the marine ecosystem.

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“…Toll-like receptor 2 (TLR2) is nearly ubiquitously expressed and mediates innate immune responses directed against a wide range of pathogens including Gram-positive bacteria, protozoa and viruses ( 10 – 12 ). Zymosan, a commonly used inducer of TLR2-mediated local inflammation, is arrested at its site of injection due to its a particulate structure.…”

Section: Introductionmentioning

confidence: 99%

Mast cell-derived interleukin-4 mediates activation of dendritic cell during toll-like receptor 2-mediated inflammation

Friedel,

Pierre,

Kolbinger

et al. 2024

Front. Immunol.

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IntroductionDuring an innate inflammation, immune cells form distinct pro- and anti-inflammatory regions around pathogen-containing core-regions. Mast cells are localized in an anti-inflammatory microenvironment during the resolution of an innate inflammation, suggesting antiinflammatory roles of these cells.MethodsHigh-content imaging was used to investigated mast cell-dependent changes in the regional distribution of immune cells during an inflammation, induced by the toll-like receptor (TLR)-2 agonist zymosan.ResultsThe distance between the zymosan-containing core-region and the anti-inflammatory region, described by M2-like macrophages, increased in mast cell-deficient mice. Absence of mast cells abolished dendritic cell (DC) activation, as determined by CD86-expression and localized the DCs in greater distance to zymosan particles. The CD86- DCs had a higher expression of the pro-inflammatory interleukins (IL)-1β and IL-12/23p40 as compared to activated CD86+ DCs. IL-4 administration restored CD86 expression, cytokine expression profile and localization of the DCs in mast cell-deficient mice. The IL-4 effects were mast cell-specific, since IL-4 reduction by eosinophil depletion did not affect activation of DCs.DiscussionWe found that mast cells induce DC activation selectively at the site of inflammation and thereby determine their localization within the inflammation. Overall, mast cells have antiinflammatory functions in this inflammation model and limit the size of the pro-inflammatory region surrounding the zymosan-containing core region.

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Expression and function of toll-like receptor 2 in vertebrate

Cited by 8 publications

References 117 publications

Meloxicam treatment disrupts the regional structure of innate inflammation sites by targeting the pro‐inflammatory effects of prostanoids

Meloxicam treatment disrupts the regional structure of innate inflammation sites by targeting the pro‐inflammatory effects of prostanoids

Internal Defense System of Mytilus galloprovincialis (Lamarck, 1819): Ecological Role of Hemocytes as Biomarkers for Thiacloprid and Benzo[a]Pyrene Pollution

Mast cell-derived interleukin-4 mediates activation of dendritic cell during toll-like receptor 2-mediated inflammation

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