scholarly journals Toll-like receptor 5 as a novel receptor for fungal zymosan

2021 ◽  
Author(s):  
Stefanie Reuter ◽  
Kristina Herold ◽  
Jana Domroes ◽  
Ralf Mrowka
Keyword(s):  
Innate Immune ◽  
Microbial Pathogens ◽  
Toll Like Receptor ◽  
Knock Out ◽  
Activation Of Transcription ◽  
Host Defense Response ◽  
Toll Like Receptor 5 ◽  
Molecular Patterns ◽  
First Time ◽  
Luciferase Reporters

Microbial pathogens carry specific structural patterns which were termed pathogenassociated molecular patterns (PAMPs). Toll-like receptors (TLRs) as key elements for the recognition of microbial pathogens are necessary for the activation of innate immune pathways. TLRs are activated by binding PAMPs of bacteria, viruses and fungi and initiate a signaling pathway resulting in the activation of transcription factors which modulate the production of various proinflammatory cytokines. It is not fully clear in detail which microbial pattern is recognized by which TLR. Here we show for the first time that TLR5 is a strong receptor for the yeast particle zymosan. We have generated stable human cell lines with combinations of TLR2 and TLR5 knock in/knock out together with stable nuclear factor kappaB (NF-κB) luciferase reporters. We found that both receptors TLR5 and TLR2 lead to an independent activation of the NF-κB pathway when simulated with zymosan. Our results demonstrate that TLR5 is a receptor for the fungal particle zymosan in addition to bacterial fragments like flagellin. Distinct cytokine patterns might suggest that TLR5 is potentially important for the differentiation in the recognition of the specific type of the foreign microorganisms and in the specific host defense response.

Toll-like receptor 5 knock-out mice exhibit a specific low level of anxiety

2021 ◽  
Author(s):  
A.M. Hamieh ◽  
G. Mallaret ◽  
M. Meleine ◽  
A. Lashermes ◽  
S. Roumeau ◽  
...  
Keyword(s):  
Toll Like Receptor ◽  
Knock Out ◽  
Low Level ◽  
Knock Out Mice ◽  
Toll Like Receptor 5

scholarly journals The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype

2018 ◽  
Author(s):  
Priya Hari ◽  
Fraser R. Millar ◽  
Nuria Tarrats ◽  
Jodie Birch ◽  
Curtis J. Rink ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Cycle Arrest ◽  
Secretory Phenotype ◽  
Immune Sensing ◽  
Molecular Patterns ◽  
Innate Immune Sensing

ABSTRACTCellular senescence is a stress response program characterised by a robust cell cycle arrest and the induction of a pro-inflammatory senescence-associated secretory phenotype (SASP) that is triggered through an unknown mechanism. Here, we show that during oncogene-induced senescence (OIS), the Toll-like receptor TLR2 and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumour suppressors p53-p21CIP1, p16INK4a and p15INK4b, and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAA) that, in turn, function as the damage associated molecular patterns (DAMPs) signalling through TLR2 in OIS. Finally, we found evidence that the cGAS-STING cytosolic DNA sensing pathway primes TLR2 and A-SAA expression in OIS. In summary, we report that innate immune sensing of senescence-associated DAMPs by TLR2 controls the SASP and reinforces the cell cycle arrest program in OIS.

scholarly journals Role of Toll-like receptor 5 in the innate immune response to acute P. aeruginosa pneumonia

2009 ◽  
Vol 297 (6) ◽  
pp. L1112-L1119 ◽  
Author(s):  
Amy E. Morris ◽  
H. Denny Liggitt ◽  
Thomas R. Hawn ◽  
Shawn J. Skerrett
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Bacterial Clearance ◽  
Toll Like Receptor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
High Inoculum ◽  
Toll Like Receptor 5

Pseudomonas aeruginosa is a leading cause of hospital-acquired pneumonia and an important pathogen in patients with chronic lung disease, such as cystic fibrosis and bronchiectasis. The contribution of Toll-like receptor 5 (TLR5) to the innate immune response to this organism is incompletely understood. We exposed wild-type and TLR5-deficient ( Tlr5−/−) mice to aerosolized P. aeruginosa at low and high inocula and assessed bacterial clearance, lung inflammation, and cytokine production 4 and 24 h after infection. Bacterial clearance was impaired in Tlr5−/−mice after low-inoculum, but not high-inoculum, infection. Early bronchoalveolar accumulation of neutrophils was reduced in Tlr5−/−mice after low- and high-dose infection. Cytokine responses, including markedly impaired monocyte chemoattractant protein-1 production 4 h after low- and high-inoculum challenge, were selectively altered in Tlr5−/−mice. In contrast, there was no impairment of bacterial clearance, neutrophil recruitment, or monocyte chemoattractant protein-1 production in Tlr5−/−mice after infection with a nonflagellated isotypic strain of P. aeruginosa . Thus TLR5-mediated recognition of flagellin is involved in activating pulmonary defenses against P. aeruginosa and contributes to antibacterial resistance in a manner that is partially inoculum dependent. These data are the first to demonstrate a unique role for TLR5 in the innate immune response to P. aeruginosa lung infection.

The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5

Nature ◽  
2001 ◽  
Vol 410 (6832) ◽  
pp. 1099-1103 ◽  
Author(s):  
Fumitaka Hayashi ◽  
Kelly D. Smith ◽  
Adrian Ozinsky ◽  
Thomas R. Hawn ◽  
Eugene C. Yi ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Toll Like Receptor 5

scholarly journals Leptospiral LPS escapes mouse TLR4 internalization and TRIF-associated antimicrobial responses through O antigen and associated lipoproteins

2020 ◽  
Author(s):  
Delphine Bonhomme ◽  
Ignacio Santecchia ◽  
Frédérique Vernel-Pauillac ◽  
Martine Caroff ◽  
Pierre Germon ◽  
...  
Keyword(s):  
Immune Escape ◽  
Severe Disease ◽  
Bacterial Pathogen ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Escape Mechanism ◽  
O Antigen ◽  
Molecular Patterns ◽  
Dependent Pathway

AbstractLeptospirosis is a worldwide re-emerging zoonosis caused by pathogenic Leptospira spp. All vertebrate species can be infected; humans are sensitive hosts whereas other species, such as rodents, may become long-term renal carrier reservoirs. Upon infection, innate immune responses are initiated by recognition of Microbial Associated Molecular Patterns (MAMPs) by Pattern Recognition Receptors (PRRs). Among MAMPs, the lipopolysaccharide (LPS) is recognized by the Toll-Like-Receptor 4 (TLR4) and activates both the MyD88-dependent pathway at the plasma membrane and the TRIF-dependent pathway after TLR4 internalization. We previously showed that leptospiral LPS is not recognized by the human TLR4, whereas it signals through murine TLR4, which mediates mouse resistance to acute leptospirosis. However, leptospiral LPS has low endotoxicity in mouse cells and is an agonist of TLR2, the sensor for bacterial lipoproteins. Here, using confocal microscopy and flow cytometry, we showed that the LPS of L. interrogans did not induce internalization of TLR4 in mouse macrophages, unlike the LPS of Escherichia coli. Consequently, the LPS failed to induce the production of the TRIF-dependent nitric oxide and RANTES, both important antimicrobial responses. Using shorter O antigen LPS and repurified leptospiral LPS with reporter HEK cells, we further found this TLR4-TRIF escape to be dependent on both the co-purifying lipoproteins and the full-length O antigen. Furthermore, our data suggest that the O antigen could alter the binding of the leptospiral LPS to the co-receptor CD14 that is essential for TLR4-TRIF activation. Overall, we describe here a novel immune escape mechanism linked to leptospiral LPS. We hypothesize that the LPS, already known as a virulence factor, plays a major role in the innate immune evasion of the leptospires, thereby contributing to their stealthiness and chronicity in mice.Author summaryLeptospira interrogans is a bacterial pathogen, responsible for leptospirosis, a worldwide neglected reemerging disease. L. interrogans may cause an acute severe disease in humans, whereas rodents and other animals asymptomatically carry the leptospires in their kidneys. They can therefore excrete live bacteria in urine and contaminate the environment. Leptospires are stealth pathogens known to escape the innate immune defenses of their hosts. They are covered in lipopolysaccharide (LPS), a bacterial motif recognized in mammals through the Toll-like receptor 4 (TLR4), which triggers two different signaling pathways. We showed previously that pathogenic leptospires escape TLR4 recognition in humans. Here we show in mice that the leptospiral LPS triggers only one arm of the TLR4 pathway and escapes the other, hence avoiding production of antimicrobial compounds. Removing the lipoproteins that always co-purify with the leptospiral LPS, or using shorter LPS, restores the stimulation of both pathways. This suggests a novel escape mechanism linked to the LPS and involving lipoproteins that could be instrumental for leptospires to escape the mouse defense and allows for their chronic renal colonization.

scholarly journals Flagellin A Toll-Like Receptor 5 Agonist as an Adjuvant in Chicken Vaccines

2014 ◽  
Vol 21 (3) ◽  
pp. 261-270 ◽  
Author(s):  
Shishir Kumar Gupta ◽  
Preety Bajwa ◽  
Rajib Deb ◽  
Madhan Mohan Chellappa ◽  
Sohini Dey
Keyword(s):  
Infectious Diseases ◽  
Immune Cells ◽  
Cytokine Production ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Vaccine Adjuvants ◽  
Toll Like Receptor ◽  
Absolute Requirement ◽  
Toll Like Receptor 5 ◽  
Potential Use

ABSTRACTChicken raised under commercial conditions are vulnerable to environmental exposure to a number of pathogens. Therefore, regular vaccination of the flock is an absolute requirement to prevent the occurrence of infectious diseases. To combat infectious diseases, vaccines require inclusion of effective adjuvants that promote enhanced protection and do not cause any undesired adverse reaction when administered to birds along with the vaccine. With this perspective in mind, there is an increased need for effective better vaccine adjuvants. Efforts are being made to enhance vaccine efficacy by the use of suitable adjuvants, particularly Toll-like receptor (TLR)-based adjuvants. TLRs are among the types of pattern recognition receptors (PRRs) that recognize conserved pathogen molecules. A number of studies have documented the effectiveness of flagellin as an adjuvant as well as its ability to promote cytokine production by a range of innate immune cells. This minireview summarizes our current understanding of flagellin action, its role in inducing cytokine response in chicken cells, and the potential use of flagellin as well as its combination with other TLR ligands as an adjuvant in chicken vaccines.

scholarly journals LPS activation of Toll-like receptor 4 signals CD11b/CD18 expression in neutrophils

2005 ◽  
Vol 288 (4) ◽  
pp. L655-L662 ◽  
Author(s):  
Ximing Zhou ◽  
Xiao-Pei Gao ◽  
Jie Fan ◽  
Qinghui Liu ◽  
Khandaker N. Anwar ◽  
...  
Keyword(s):  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Cd11b Expression ◽  
Lps Challenge ◽  
Activation Of Transcription ◽  
Signaling Function ◽  
Host Defense Response ◽  
Lps Activation ◽  
Made In

We identify herein a novel signaling function of the Toll-like receptor-4 (TLR4), the lipopolysaccharide (LPS) receptor mediating the innate immune response, in inducing the expression of CD11b/CD18 integrin in polymorphonuclear leukocytes (PMNs). Studies were made in PMNs isolated from TLR4-deficient (TLR4−/−) and C57BL/6 [wild-type (WT)] mice. We observed increased CD11b expression in WT PMNs within 3 h after LPS challenge, whereas CD11b was not expressed in TLR4−/− PMNs above basal levels. TLR4-activated CD11b expression was cycloheximide sensitive and involved the activation of transcription factors, NF-κB and c-Jun/PU.1. TLR4−/− PMNs challenged with LPS were functionally defective as the result of the impaired CD11b expression in that they failed to adhere and did not migrate across endothelial cells in response to N-formylmethionyl-leucyl-phenylalanine. TLR4 also promoted increased binding of LPS to PMNs on the basis of expression of CD11b. Thus TLR4 signaling activates synthesis and upregulation of CD11b and is essential for PMN adhesion and transmigration. Our data suggest an important role of TLR4-activated CD11b expression in the mechanism of the PMN host-defense response to LPS.

scholarly journals Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Se Jin Park ◽  
Jee Youn Lee ◽  
Sang Jeong Kim ◽  
Se-Young Choi ◽  
Tae Young Yune ◽  
...  
Keyword(s):  
Immune System ◽  
Social Withdrawal ◽  
Lipoteichoic Acid ◽  
Innate Immune ◽  
Psychotic Symptoms ◽  
Toll Like Receptor ◽  
Knock Out ◽  
Biochemical Alterations ◽  
Toll Like Receptor 2 ◽  
The Brain

Abstract Dysregulation of the immune system contributes to the pathogenesis of neuropsychiatric disorders including schizophrenia. Here, we demonstrated that toll-like receptor (TLR)-2, a family of pattern-recognition receptors, is involved in the pathogenesis of schizophrenia-like symptoms. Psychotic symptoms such as hyperlocomotion, anxiolytic-like behaviors, prepulse inhibition deficits, social withdrawal and cognitive impairments were observed in TLR-2 knock-out (KO) mice. Ventricle enlargement, a hallmark of schizophrenia, was also observed in TLR-2 KO mouse brains. Levels of p-Akt and p-GSK-3α/β were markedly higher in the brain of TLR-2 KO than wild-type (WT) mice. Antipsychotic drugs such as haloperidol or clozapine reversed behavioral and biochemical alterations in TLR-2 KO mice. Furthermore, p-Akt and p-GSK-3α/β were decreased by treatment with a TLR-2 ligand, lipoteichoic acid, in WT mice. Thus, our data suggest that the dysregulation of the innate immune system by a TLR-2 deficiency may contribute to the development and/or pathophysiology of schizophrenia-like behaviors via Akt-GSK-3α/β signaling.

scholarly journals Battle Royale: Innate Recognition of Poxviruses and Viral Immune Evasion

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 765
Author(s):  
Huibin Yu ◽  
Ryan C. Bruneau ◽  
Greg Brennan ◽  
Stefan Rothenburg
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Immune Defense ◽  
Innate Immune ◽  
Host Immune Responses ◽  
Antiviral Responses ◽  
Activation Of Transcription ◽  
Immune Sensing ◽  
Molecular Patterns ◽  
Innate Immune Sensing

Host pattern recognition receptors (PRRs) sense pathogen-associated molecular patterns (PAMPs), which are molecular signatures shared by different pathogens. Recognition of PAMPs by PRRs initiate innate immune responses via diverse signaling pathways. Over recent decades, advances in our knowledge of innate immune sensing have enhanced our understanding of the host immune response to poxviruses. Multiple PRR families have been implicated in poxvirus detection, mediating the initiation of signaling cascades, activation of transcription factors, and, ultimately, the expression of antiviral effectors. To counteract the host immune defense, poxviruses have evolved a variety of immunomodulators that have diverse strategies to disrupt or circumvent host antiviral responses triggered by PRRs. These interactions influence the outcomes of poxvirus infections. This review focuses on our current knowledge of the roles of PRRs in the recognition of poxviruses, their elicited antiviral effector functions, and how poxviral immunomodulators antagonize PRR-mediated host immune responses.

scholarly journals The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype

2019 ◽  
Vol 5 (6) ◽  
pp. eaaw0254 ◽  
Author(s):  
Priya Hari ◽  
Fraser R. Millar ◽  
Nuria Tarrats ◽  
Jodie Birch ◽  
Andrea Quintanilla ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Cycle Arrest ◽  
Toll Like Receptor 2 ◽  
Secretory Phenotype ◽  
Immune Sensing ◽  
Molecular Patterns

Cellular senescence is a stress response program characterized by a robust cell cycle arrest and the induction of a proinflammatory senescence-associated secretory phenotype (SASP) that is triggered through an unknown mechanism. Here, we show that, during oncogene-induced senescence (OIS), the Toll-like receptor 2 (TLR2) and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumor suppressors p53-p21CIP1, p16INK4a, and p15INK4b and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAAs) that, in turn, function as the damage-associated molecular patterns (DAMPs) signaling through TLR2 in OIS. Last, we found evidence that the cGAS-STING cytosolic DNA sensing pathway primes TLR2 and A-SAAs expression in OIS. In summary, we report that innate immune sensing of senescence-associated DAMPs by TLR2 controls the SASP and reinforces the cell cycle arrest program in OIS.

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