The WNT Signaling Pathway Contributes to Dectin-1-Dependent Inhibition of Toll-Like Receptor-Induced Inflammatory Signature

Trinath, Jamma; Holla, Sahana; Mahadik, Kasturi; Prakhar, Praveen; Singh, Vikas; Balaji, Kithiganahalli Narayanaswamy

doi:10.1128/mcb.00641-14

Cited by 44 publications

(38 citation statements)

References 55 publications

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“…In peritoneal macrophages, Socs1 and PIAS1 induction downstream of Dectin-1 has been described in a Ca 2+ -dependent manner to be dependent on the expression of Wnt5a, induced by the ROS/b-catenin axis. Socs1 and PIAS1 induction lead to reduced expression of IL-12, IL-1b, and TNF and abrogated TLR signaling via degradation of IL-1R-associated kinase (IRAK)1, IRAK4, and MyD88 (151). Downstream of Dectin-2, but not of Dectin-1, b-catenin stabilization in DCs occurs dependent on phosphorylation of LAB and leads to impaired IL-12 production (152).…”

Section: Conflicting Signaling Of Clrs: Negative Regulationmentioning

confidence: 99%

Contact, Collaboration, and Conflict: Signal Integration of Syk-Coupled C-Type Lectin Receptors

Ostrop

Lang

2017

The Journal of Immunology

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conducted on CLR assigned to the so-called Dectin-1 or Dectin-2 clusters, localized within 51 the NK cell gene cluster on human chromosome 12 or mouse chromosome 6 (1-3). Several 52 excellent reviews on the function of these CLR in anti-microbial defense and homeostasis are 53 available (4, 5). In this review we summarize the current knowledge about signaling 54 downstream of the activating CLR Dectin-1 (Clec7a), Dectin-2 (human Clec6a, mouse 55 Clec4n), Mincle (Clec4e) and Mcl (Clec4d) that is largely dependent on the kinase spleen 56 tyrosine kinase (Syk). Table I provides an overview of defined ligands and microorganisms 57 bound by this group of PRR. In addition to microbial carbohydrate and glycolipid structures 58 acting as PAMP, several CLR bind endogenous ligands such as SAP130 released by dying 59 cells or cholesterol crystals. Thus, these CLR are involved in homeostatic responses and 60 inflammatory conditions (6-9), in addition to host response to pathogens and commensals (10-61 (Fig. 1). 103 Syk-Card9 coupled CLR is observed across cell-types and species, promoting the 111 differentiation of IL-17-producing CD4+ T cells (23, 24, 26, 27). Remarkably, to date there is 112 only very limited information about the effects of combined stimulation of CLR and TLR 113 pathways on global gene expression. 114

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Section: Conflicting Signaling Of Clrs: Negative Regulationmentioning

confidence: 99%

Contact, Collaboration, and Conflict: Signal Integration of Syk-Coupled C-Type Lectin Receptors

Ostrop

Lang

2017

The Journal of Immunology

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“…Notably, the authors show that the induction of Wnt5a is also dependent on the presence of TLRs. Also engagement of the C-type lectin dectin-1 was shown to drive Wnt5a formation in macrophages (63). In addition to human and murine cells, an increased expression of Wnt5a was also observed in Mycobacterium marinum -infected adult zebrafish (64), demonstrating that induction of Wnt5a upon infection is a conserved mechanism.…”

Section: Wnt Signaling Promoting Inflammation - Wnt5amentioning

confidence: 99%

The Wnt Blows: On the Functional Role of Wnt Signaling in Mycobacterium tuberculosis Infection and Beyond

Brandenburg

Reiling

2016

Front. Immunol.

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In recent years, it has become apparent that the Wnt signaling pathway, known for its essential functions in embryonic development and tissue homeostasis, exerts immunomodulatory functions during inflammation and infection. Most functional studies indicate that Wnt5a exerts pro-inflammatory functions on its cellular targets, which include various types of immune and non-immune cells. Wnt5a expression has also been linked to the pathogenesis of chronic inflammatory diseases. Activation of beta-catenin-dependent Wnt signaling, e.g., by Wnt3a, has however been shown to limit inflammation by interfering with the nuclear factor kappa-light chain-enhancer of activated B-cells (NF-kappaB) pathway. This review focuses on the regulation of Wnt5a, Wnt3a, and the recently identified Wnt6 and their functional role in bacterial infections with a primary focus on pulmonary tuberculosis, a leading infectious cause of morbidity and mortality worldwide.

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“…SOCS-1 suppresses a multitude of signaling molecules, such as the Mal adaptor protein in TLR4 signaling (83), IRAK-4 (84), TRAF6 (85), type I IFNs (30, 58), JAKs (86) and transcriptional promoters including STAT-1 (58, 87), IRF7 (88) and p53 (89). Importantly, Socs-1 knockdown in Japanese encephalitis virus (JEV)-infected macrophages resulted in reduced viral load and increased ISGs, suggesting that SOCS-1 may directly regulate expression of ISGs (90).…”

Section: Discussionmentioning

confidence: 99%

TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice

Paul

Acharya

et al. 2016

The Journal of Immunology

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West Nile virus (WNV) is a neurotropic, single-stranded RNA (ssRNA) flavivirus that can cause encephalitis, meningitis, and death in humans and mice. Human Toll-like receptor (TLR) 7, 8, and mouse TLR7 recognize viral ssRNA motifs and induce antiviral immunity. However, the role of mouse TLR8 in antiviral immunity is poorly understood. Here, we report that TLR8 deficient (Tlr8−/−) mice were resistant to WNV infection compared to wild-type (WT) controls. Efficient WNV clearance and moderate susceptibility to WNV-mediated neuronal death in Tlr8−/− mice was attributed to overexpression of Tlr7 and an interferon-stimulated gene Isg-56 expression, while reduced expression of the pro-apoptotic gene coding Bcl2-associated X protein (Bax) was observed. Interestingly, suppressor of cytokine signaling -1 (SOCS-1) directly associated with TLR8, but not with TLR7, indicating a novel role for TLR8 regulation of SOCS-1 function, while selective siRNA knockdown of Socs-1 resulted in induced Isg-56 and Tlr7 expression following WNV infection. Collectively, we report that TLR8 coupling with SOCS-1 inhibits TLR7-mediated antiviral immunity during WNV infection in mice.

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The WNT Signaling Pathway Contributes to Dectin-1-Dependent Inhibition of Toll-Like Receptor-Induced Inflammatory Signature

Cited by 44 publications

References 55 publications

Contact, Collaboration, and Conflict: Signal Integration of Syk-Coupled C-Type Lectin Receptors

Contact, Collaboration, and Conflict: Signal Integration of Syk-Coupled C-Type Lectin Receptors

The Wnt Blows: On the Functional Role of Wnt Signaling in Mycobacterium tuberculosis Infection and Beyond

TLR8 Couples SOCS-1 and Restrains TLR7-Mediated Antiviral Immunity, Exacerbating West Nile Virus Infection in Mice

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