The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2

Skjesol, Astrid; Yurchenko, Mariya; Bösl, Korbinian; Gravastrand, Caroline S.; Nilsen, Kaja Elisabeth; Grøvdal, Lene Melsæther; Agliano, Federica; Patanè, Francesco; Lentini, Germana; Kim, Hera; Teti, Giuseppe; Sharma, Aditya Kumar; Kandasamy, Richard K.; Sporsheim, Bjørnar; Starheim, Kristian K.; Golenbock, Douglas T.; Stenmark, Harald; McCaffrey, Mary W.; Espevik, Terje; Husebye, Harald

doi:10.1371/journal.ppat.1007684

Cited by 29 publications

(36 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, unusual Rab11-dependent trafficking of an intracellular pool of TLR4 bypassing its plasma membrane localization was detected during phagocytosis of E. coli by human monocytes (Fig. 2, VI) [95,187]. Rab11-positive vesicles also carry TRAM to the phagosomes, while in LPS-stimulated cells they participate in transporting GOLD domain-containing proteins to TLR4/LPS-harboring endosomes, thereby affecting the duration of the TRIFdependent signaling [181,182].…”

Section: Intracellular Trafficking Of Tlr4: An Overviewmentioning

confidence: 95%

TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling

Ciesielska

Matyjek

Kwiatkowska

2020

Cell. Mol. Life Sci.

722

466

View full text Add to dashboard Cite

Toll-like receptor (TLR) 4 belongs to the TLR family of receptors inducing pro-inflammatory responses to invading pathogens. TLR4 is activated by lipopolysaccharide (LPS, endotoxin) of Gram-negative bacteria and sequentially triggers two signaling cascades: the first one involving TIRAP and MyD88 adaptor proteins is induced in the plasma membrane, whereas the second engaging adaptor proteins TRAM and TRIF begins in early endosomes after endocytosis of the receptor. The LPS-induced internalization of TLR4 and hence also the activation of the TRIF-dependent pathway is governed by a GPI-anchored protein, CD14. The endocytosis of TLR4 terminates the MyD88-dependent signaling, while the following endosome maturation and lysosomal degradation of TLR4 determine the duration and magnitude of the TRIF-dependent one. Alternatively, TLR4 may return to the plasma membrane, which process is still poorly understood. Therefore, the course of the LPS-induced pro-inflammatory responses depends strictly on the rates of TLR4 endocytosis and trafficking through the endo-lysosomal compartment. Notably, prolonged activation of TLR4 is linked with several hereditary human diseases, neurodegeneration and also with autoimmune diseases and cancer. Recent studies have provided ample data on the role of diverse proteins regulating the functions of early, late, and recycling endosomes in the TLR4-induced inflammation caused by LPS or phagocytosis of E. coli. In this review, we focus on the mechanisms of the internalization and intracellular trafficking of TLR4 and CD14, and also of LPS, in immune cells and discuss how dysregulation of the endo-lysosomal compartment contributes to the development of diverse human diseases.

show abstract

Section: Intracellular Trafficking Of Tlr4: An Overviewmentioning

confidence: 95%

TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling

Ciesielska

Matyjek

Kwiatkowska

2020

Cell. Mol. Life Sci.

722

466

View full text Add to dashboard Cite

show abstract

“…After bacterial recognition, TLR4 initially recruits TIRAP and MyD88 and then activates NF- κ B and p38 MAPK via interleukin-1 receptor-associated kinases (IRAKs), TNF receptor-associated factor 6 (TRAF6), and TGF beta-activated kinase 1 (TAK1) complexes [ 122 , 136 – 141 ] ( Figure 1 ). Furthermore, TLR4 is endocytosed to the Rab11a-positive phagosome to form a complex with TRAM and TRIF, which then activates the TRAF3-TANK-binding kinase 1 (TBK1)-IRF3 axis to induce expression of type I IFN [ 142 , 143 ] ( Figure 1 ).…”

Section: Innate Immune Recognition Mechanisms In Pulmonary Infectimentioning

confidence: 99%

The Role of Innate Immunity in Pulmonary Infections

Zhang

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

Innate immunity forms a protective line of defense in the early stages of pulmonary infection. The primary cellular players of the innate immunity against respiratory infections are alveolar macrophages (AMs), dendritic cells (DCs), neutrophils, natural killer (NK) cells, and innate lymphoid cells (ILCs). They recognize conserved structures of microorganisms through membrane-bound and intracellular receptors to initiate appropriate responses. In this review, we focus on the prominent roles of innate immune cells and summarize transmembrane and cytosolic pattern recognition receptor (PRR) signaling recognition mechanisms during pulmonary microbial infections. Understanding the mechanisms of PRR signal recognition during pulmonary pathogen infections will help us to understand pulmonary immunopathology and lay a foundation for the development of effective therapies to treat and/or prevent pulmonary infections.

show abstract

“…3). 132 Taken together, these studies uncover a molecule-specific role of lumican in promoting TLR4-and CD14-dependent pathogen sensing. 3,126 Besides its effect on TLR4-mediated pathogen recognition, lumican modulates inflammatory response by regulating Fas ligand (FasL)-Fas signaling (Fig.…”

Section: Mechanisms Of Lumican-dependent Regulation Of Inflammationmentioning

confidence: 85%

Communications via the Small Leucine-rich Proteoglycans: Molecular Specificity in Inflammation and Autoimmune Diseases

Zeng-Brouwers

Pandey

Trebicka

et al. 2020

J Histochem Cytochem.

View full text Add to dashboard Cite

Inflammation is a highly regulated biological response of the immune system that is triggered by assaulting pathogens or endogenous alarmins. It is now well established that some soluble extracellular matrix constituents, such as small leucine-rich proteoglycans (SLRPs), can act as danger signals and trigger aseptic inflammation by interacting with innate immune receptors. SLRP inflammatory signaling cascade goes far beyond its canonical function. By choosing specific innate immune receptors, coreceptors, and adaptor molecules, SLRPs promote a switch between pro- and anti-inflammatory signaling, thereby determining disease resolution or chronification. Moreover, by orchestrating signaling through various receptors, SLRPs fine-tune inflammation and, despite their structural homology, regulate inflammatory processes in a molecule-specific manner. Hence, the overarching theme of this review is to highlight the molecular and functional specificity of biglycan-, decorin-, lumican-, and fibromodulin-mediated signaling in inflammatory and autoimmune diseases

show abstract

The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2

Cited by 29 publications

References 52 publications

TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling

TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling

The Role of Innate Immunity in Pulmonary Infections

Communications via the Small Leucine-rich Proteoglycans: Molecular Specificity in Inflammation and Autoimmune Diseases

Contact Info

Product

Resources

About