Pam3CSK4/TLR2 signaling elicits neutrophil recruitment and restricts invasion of Escherichia coli P4 into mammary gland epithelial cells in a murine mastitis model

Mintz, Michal; Mintz, Dvir; Ilia-Ezra, Raaya; Shpigel, Nahum Y.

doi:10.1016/j.vetimm.2012.09.030

Cited by 16 publications

(14 citation statements)

References 21 publications

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“…Some mammary epithelial tissue exposure experiments have described an effect of LPS and LTA on the innate immune response, but how these key virulence factors modulate the mammary gland microenvironment has been scarcely studied in vitro and especially in vivo (16, 27, 32). The validated murine intramammary inoculation model previously demonstrated that local macrophages are of key importance for the LPS–TLR4 axis-mediated neutrophil recruitment into the alveolar lumen, while this is far less the case for TLR2-mediated signaling (27, 62). In general, macrophages can be programmed to different priming and tolerance states by varying dosages of LPS (63).…”

Section: Discussionmentioning

confidence: 99%

Preconditioning with Lipopolysaccharide or Lipoteichoic Acid Protects against Staphylococcus aureus Mammary Infection in Mice

et al. 2017

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Staphylococcus aureus is one of the most causative agents of mastitis and is associated with chronic udder infections. The persistency of the pathogen is believed to be the result of an insufficient triggering of local inflammatory signaling. In this study, the preclinical mastitis model was used, aiming to evaluate if lipopolysaccharide (LPS) or lipoteichoic acid (LTA) preconditioning could aid the host in more effectively clearing or at least limiting a subsequent S. aureus infection. A prototypic Gram-negative virulence factor, i.e., LPS and Gram-positive virulence factor, i.e., LTA were screened whether they were able to boost the local immune compartment. Compared to S. aureus-induced inflammation, both toxins had a remarkable high potency to efficiently induce two novel selected innate immunity biomarkers i.e., lipocalin 2 (LCN2) and chitinase 3-like 1 (CHI3L1). When combining mammary inoculation of LPS or LTA prior to a local S. aureus infection, we were able to modulate the innate immune response, reduce local bacterial loads, and induce either LCN2 or CHI3L1 at 24 h post-infection. Clodronate depletion of mammary macrophages also identified that macrophages contribute only to a limited extend to the LPS/LTA-induced immunomodulation upon S. aureus infection. Based on histological neutrophil influx evaluation, concomitant local cytokine profiles and LCN2/CHI3L1 patterns, the macrophage-independent signaling plays a major role in the LPS- or LTA-pretreated S. aureus-infected mouse mammary gland. Our results highlight the importance of a vigilant microenvironment during the innate immune response of the mammary gland and offer novel insights for new approaches concerning effective immunomodulation against a local bacterial infection.

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Section: Discussionmentioning

confidence: 99%

Preconditioning with Lipopolysaccharide or Lipoteichoic Acid Protects against Staphylococcus aureus Mammary Infection in Mice

et al. 2017

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“…Certain Lactobacillus strains may exert anti-inflammatory effects via TLR2 activation (29,30). In addition, activation of TLR2 signaling was shown to induce neutrophil recruitment and restrict invasion of E. coli P4 into mammary gland epithelial cells in a murine mastitis model (31). Based on these results, we hypothesize that L. rhamnosus GR-1-mediated activation of TLR2-dependent signaling may induce recruitment and activation of inflammatory cells, representing an important primary line of host defense in E. coli-induced mastitis.…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus rhamnosus GR-1 Ameliorates Escherichia coli-Induced Inflammation and Cell Damage via Attenuation of ASC-Independent NLRP3 Inflammasome Activation

Liu

Yang

et al. 2016

Appl Environ Microbiol

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Escherichia coli is a major environmental pathogen causing bovine mastitis, which leads to mammary tissue damage and cell death. We explored the effects of the probiotic Lactobacillus rhamnosus GR-1 on ameliorating E. coli-induced inflammation and cell damage in primary bovine mammary epithelial cells (BMECs). Increased Toll-like receptor 4 (TLR4), NOD1, and NOD2 mRNA expression was observed following E. coli challenge, but this increase was attenuated by L. rhamnosus GR-1 pretreatment. Immunofluorescence and Western blot analyses revealed that L. rhamnosus GR-1 pretreatment decreased the E. coli-induced increases in the expression of the NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3) and the serine protease caspase 1. However, expression of the adaptor protein apoptosis-associated speck-like protein (ASC, encoded by the Pycard gene) was decreased during E. coli infection, even with L. rhamnosus GR-1 pretreatment. Pretreatment with L. rhamnosus GR-1 counteracted the E. coli-induced increases in interleukin-1␤ (IL-1␤), -6, -8, and -18 and tumor necrosis factor alpha mRNA expression but upregulated IL-10 mRNA expression. Our data indicate that L. rhamnosus GR-1 reduces the adhesion of E. coli to BMECs, subsequently ameliorating E. coli-induced disruption of cellular morphology and ultrastructure and limiting detrimental inflammatory responses, partly via promoting TLR2 and NOD1 synergism and attenuating ASC-independent NLRP3 inflammasome activation. Although the residual pathogenic activity of L. rhamnosus, the dosage regimen, and the means of probiotic supplementation in cattle remain undefined, our data enhance our understanding of the mechanism of action of this candidate probiotic, allowing for development of specific probiotic-based therapies and strategies for preventing pathogenic infection of the bovine mammary gland. Mastitis affects cows in all regions of the world and can cause a decrease in milk production and quality, resulting in a major economic burden to the dairy industry (1). Escherichia coli is by far the most common cause of mastitis, since it is isolated in more than 80% of cases of coliform mastitis (2). Antibiotic therapy frequently leaves residues in milk, potentially facilitating the development of antibiotic resistance. Probiotics represent a novel alternative to antibiotics for controlling pathogen infections.Lactobacillus rhamnosus GR-1 is a probiotic bacterium isolated from the female urethra, and oral ingestion of L. rhamnosus GR-1 and L. fermentum RC-14 reduces vaginal colonization by pathogenic bacteria and yeasts and maintains urogenital health in women (3). Pretreatment of pregnant CD-1 mice with L. rhamnosus GR-1 culture supernatant decreases lipopolysaccharide (LPS)-induced production of various cytokines and chemokines (4). Lactobacillus rhamnosus GR-1 suppresses expression of nuclear factor (NF)-B-related inflammatory genes and activates alternate mitogen-activated protein kinase (MAPK) and activator protein 1 pathways to recruit host defense factors...

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“…Specific TLR ligands were added to cell medium 1 day before the measurement of oxidative parameters. The concentrations assayed have been shown to affect the activity of epithelial cells (Mendoza et al 2009(Mendoza et al , 2012Mintz et al 2013). TNFα treatment at 5 ng/ml was used as a reference of prooxidant condition (Al-Shudiefat et al 2013).…”

Section: Methodsmentioning

confidence: 99%

TLR2, TLR3, and TLR4 activation specifically alters the oxidative status of intestinal epithelial cells

Latorre

Mendoza

Layunta

et al. 2014

Cell Stress and Chaperones

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Intestinal inflammatory diseases are the result of multiple processes, including mucosal oxidative stress and perturbed homeostasis between commensal bacteria and mucosal immunity. Toll-like receptors (TLRs) recognize molecular-associated microorganisms' patterns and trigger innate immunity responses contributing to intestinal homeostasis and inflammatory responses. However, TLRs effects on redox balance in intestinal mucosa remain unknown. Therefore, the present study analyzes the effect of TLR2, TLR3, and TLR4 on both oxidative damage of lipids and proteins, and the activity of antioxidant enzymes in enterocyte-like Caco-2 cells. The results show that the activation of these TLRs increased lipid and protein oxidation levels; however, the effect on the antioxidant enzymes activity is different depending on the TLR activated. These results suggest that the activation of TLR2, TLR3, and TLR4 might affect intestinal inflammation by not only their inherent innate immunity responses, but also their pro-oxidative effects on intestinal epithelial cells.

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Pam3CSK4/TLR2 signaling elicits neutrophil recruitment and restricts invasion of Escherichia coli P4 into mammary gland epithelial cells in a murine mastitis model

Cited by 16 publications

References 21 publications

Preconditioning with Lipopolysaccharide or Lipoteichoic Acid Protects against Staphylococcus aureus Mammary Infection in Mice

Preconditioning with Lipopolysaccharide or Lipoteichoic Acid Protects against Staphylococcus aureus Mammary Infection in Mice

Lactobacillus rhamnosus GR-1 Ameliorates Escherichia coli-Induced Inflammation and Cell Damage via Attenuation of ASC-Independent NLRP3 Inflammasome Activation

TLR2, TLR3, and TLR4 activation specifically alters the oxidative status of intestinal epithelial cells

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