The C-Type Lectin Receptor DC-SIGN Has an Anti-Inflammatory Role in Human M(IL-4) Macrophages in Response to Mycobacterium tuberculosis

Lugo-Villarino, Geanncarlo; Troegeler, Anthony; Balboa, Luciana; Lastrucci, Claire; Duval, Carine; Mercier, Ingrid; Bénard, Alan; Capilla, Florence; Saati, Talal Al; Poincloux, Renaud; Kondova, Ivanela; Verreck, Frank A. W.; Cougoule, Céline; Maridonneau‐Parini, Isabelle; Sasiain, Marı́a del Carmen; Neyrolles, Olivier

doi:10.3389/fimmu.2018.01123

Cited by 63 publications

(46 citation statements)

References 57 publications

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“…The siRNA gene silencing in BV2 cells was performed as previously described [32]. Briefly, BV2 cells were seeded into a 6-well plate (Corning Inc.) at a density of 1.5 × 10 5 cells/well 24 h prior to transfection.…”

Section: Rna Interference Experimentsmentioning

confidence: 99%

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

et al. 2020

J Neuroinflammation

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Background: Dendritic cell-associated C-type lectin-1 (Dectin-1) receptor has been reported to be involved in neuroinflammation in Alzheimer's disease and traumatic brain injury. The present study was designed to investigate the role of Dectin-1 and its downstream target spleen tyrosine kinase (Syk) in early brain injury after ischemic stroke using a focal cortex ischemic stroke model. Methods: Adult male C57BL/6 J mice were subjected to a cerebral focal ischemia model of ischemic stroke. The neurological score, adhesive removal test, and foot-fault test were evaluated on days 1, 3, 5, and 7 after ischemic stroke. Dectin-1, Syk, phosphorylated (p)-Syk, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expression was analyzed via western blotting in ischemic brain tissue after ischemic stroke and in BV2 microglial cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro. The brain infarct volume and Iba1-positive cells were evaluated using Nissl's and immunofluorescence staining, respectively. The Dectin-1 antagonist laminarin (LAM) and a selective inhibitor of Syk phosphorylation (piceatannol; PIC) were used for the intervention. Results: Dectin-1, Syk, and p-Syk expression was significantly enhanced on days 3, 5, and 7 and peaked on day 3 after ischemic stroke. The Dectin-1 antagonist LAM or Syk inhibitor PIC decreased the number of Iba1-positive cells and TNF-α and iNOS expression, decreased the brain infarct volume, and improved neurological functions on day 3 after ischemic stroke. In addition, the in vitro data revealed that Dectin-1, Syk, and p-Syk expression was increased following the 3-h OGD and 0, 3, and 6 h of reperfusion in BV2 microglial cells. LAM and PIC also decreased TNF-α and iNOS expression 3 h after OGD/R induction. Conclusion: Dectin-1/Syk signaling plays a crucial role in inflammatory activation after ischemic stroke, and further investigation of Dectin-1/Syk signaling in stroke is warranted.

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Section: Rna Interference Experimentsmentioning

confidence: 99%

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

et al. 2020

J Neuroinflammation

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“…18 A recent report showed that silencing DC-SIGN on IL-4treated human monocyte-derived macrophages enhances M. tuberculosis-induced pro-inflammatory cytokine production. 19 These findings showed that DC-SIGN expression on myeloid cells affects the pathogenesis of mycobacterial infection. However, how the expression of DC-SIGN in non-immune cells impacts the pathogenic mechanism of an infection has never been investigated.…”

Section: Introductionmentioning

confidence: 90%

Human dendritic cell-specific ICAM-3-grabbing non-integrin downstream signaling alleviates renal fibrosis via Raf-1 activation in systemic candidiasis

Chen

Lin

et al. 2018

Cell Mol Immunol

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We generated a human dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) transgenic mouse in which renal tubular epithelial cells expressed DC-SIGN. The transgenic mice were infected with Candida albicans intravenously to study how DC-SIGN expression affected the pathogenesis of systemic candidiasis. We discovered that, while C. albicans infection induced renal fibrosis in both transgenic and littermate control mice, the transgenic mice had significantly lower levels of Acta2, Col1a2, Col3a1, and Col4a1 mRNA transcripts compared to the controls. KIM-1, an emerging biomarker for kidney injury, along with Tnf, Il6, and Tgfb1 transcripts, were lower in infected transgenic mice, and yet, the levels of Il10 remained comparable to the controls. While renal CD45 infiltrating cells were the source of Tnf, Il6, and Il10, LTL renal proximal tubular epithelial cells were TGF-β1 producers in both infected transgenic and littermate controls. DC-SIGN-expressing tubular epithelial cells produced less TGF-β1 in response to C. albicans infection. In vivo experiments demonstrated that renal proximal tubular epithelial cell production of TGF-β1 was key to C. albicans-induced renal fibrosis and injury. Infection of transgenic mice induced a marked increase of phosphorylated Raf-1 and p38 in the kidney. However, ERK1/2 and JNK phosphorylation was more pronounced in the infected-littermate controls. Interestingly, treating the infected transgenic mice with a Raf-1 inhibitor increased the levels of the Tgfb1, Kim1, and Acta2 transcripts. These results indicate that DC-SIGN signaling, through activation of Raf-1 and p38 and suppression of JNK and ERK1/2 phosphorylation, reduces TGF-β1 production and C. albicans-induced renal fibrosis. Our study reveals for the first time the effect of DC-SIGN expression on C. albicans-induced renal fibrosis.

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“…В отсутствие этого белка IL-4-активированные макрофаги проявляли провоспалительный фенотип при заражении M. tuberculosis и приобретали лучшую способность контролировать внутриклеточный рост этого патогена. Однако в отсутствие DC-SIGN при туберкулезной инфекции отмечалось снижение восстановления и ремоделирования тканей -процессов, являющихся характерными функциональными проявлениями деятельности альтернативно активированных макрофагов [61].…”

Section: Dc-signunclassified

Innate immune receptors in development of Mycobacterium tuberculosis infection

Лапштаева

Живечкова

Сычев

et al. 2020

Russian Journal of Infection and Immunity

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According to the World Health Organization, over 10 million new tuberculosis cases are reported annually worldwide. According to the 2017 Federal State Statistics Service Report, incidence rate for active TB infection in the Russian Federation was 109.8 cases per 100,000 population, of which 41.3% accounted for chronic disease form. Regardless of climatic conditions, high prevalence of TB infection, is not only due to high Mycobacterium tuberculosis viability, but also its ability for long persistence in human body and reactivation after an unlimited period of dormancy. The outcome of infection is largely determined by host immunoreactivity and its ability to develop protective immune response. In addition, status of immune system also underlies tuberculosis course after the onset: either as a localized form, or as a form with extensive damage to the lungs and even other organs observed in generalized infection. In recent decades, a great attention was paid to examining mechanisms of adaptive cell immunity played in pathogenesis of TB infection. No doubt, adaptive immunity is a powerful defense system providing a targeted specific immune response, but now it is becoming clear that it represents solely an effector arm of innate immunity. Innate immunity is a phylogenetically more ancient, inherited system largely aimed at ensuring rapid pathogen elimination and preventing development of infection at early stages when adaptive immunity ongoing antigen-specific maturation. Mechanisms of innate immunity mediated by cells, diverse receptors, molecules and their complexes, found on various cells. Activation of innate immunity begins with recognition of conserved molecular groups present in various pathogens called pathogen-associated molecular patterns (PAMPs), which are sensed by pathogen recognition receptors (PRRs). Here, we review current data on the role of innate receptors in recognizing M. tuberculosis-derived PAMPs, production of immunoregulatory cytokines and activation of signaling pathways playing a crucial role in the regulation of necroptosis, apoptosis and autophagy of infected macrophages. Significance of innate mucosal factors in implementing immune response to M. tuberculosis is discussed. In particular, Toll-like receptors, scavenger-receptors, mannose receptor, DC-SIGN etc. were described to participate in development of M. tuberculosis immunity. The data on single nucleotide polymorphic variants for innate genes are shown, which predispose to developing tuberculosis and affecting its course.

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The C-Type Lectin Receptor DC-SIGN Has an Anti-Inflammatory Role in Human M(IL-4) Macrophages in Response to Mycobacterium tuberculosis

Cited by 63 publications

References 57 publications

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

Dectin-1/Syk signaling triggers neuroinflammation after ischemic stroke in mice

Human dendritic cell-specific ICAM-3-grabbing non-integrin downstream signaling alleviates renal fibrosis via Raf-1 activation in systemic candidiasis

Innate immune receptors in development of Mycobacterium tuberculosis infection

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