Macrophage-Inducible C-Type Lectin Mincle-Expressing Dendritic Cells Contribute to Control of Splenic Mycobacterium bovis BCG Infection in Mice

Behler, Friederike; Maus, Regina; Bohling, Jennifer; Knippenberg, Sarah; Kirchhof, Gabriele; Nagata, Michio; Jonigk, Danny; Izykowski, Nicole; Mägel, Lavinia; Welte, Tobias; Yamasaki, Satoshi; Maus, Ulrich A.

doi:10.1128/iai.02500-14

Cited by 40 publications

(32 citation statements)

References 38 publications

(19 reference statements)

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“…Mincle expression has been shown to be important in susceptibility to both mycobacterial and fungal infections (19, 38, 39) and in sensing danger signals such as the endogenous protein SAP130 (40), thereby implicating multiple pathogenic mechanisms by which it could contribute to disease. Activation of Mincle by TDB sufficiently reproduced the EAU disease phenotype, a response that required Mincle and Card9 expression as well as Syk activity.…”

Section: Discussionmentioning

confidence: 99%

Mincle Activation and the Syk/Card9 Signaling Axis Are Central to the Development of Autoimmune Disease of the Eye

Lee

Brown

Vance

et al. 2016

The Journal of Immunology

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Uveitis, which occurs in association with systemic immunological diseases, presents a considerable medical challenge due to incomplete understanding of its pathogenesis. The signals that initiate T cells to target the eye, which may be of infectious or non-infectious origin, are poorly understood. Experimental autoimmune uveoretinitis (EAU) develops in mice immunized with the endogenous retinal protein interphotoceptor retinoid binding protein (IRBP) in the presence of the adjuvant CFA. EAU manifests as posterior ocular inflammation consisting of vasculitis, granulomas, retinal damage and invasion of self-reactive T cells, which are key clinical features of human uveitis. Our studies uncover Card9 as a critical genetic determinant for EAU. Card9 was responsible for Th17 polarization and Th17-associated antigen-specific responses, but not Th1-associated responses. Nonetheless, Card9 expression was essential for accumulation of both lineages within the eye. Consistent with its recently identified role as an intracellular signaling mediator for C-type lectin receptors (CLRs), a Card9-dependent transcriptional response in the neuroretina was observed involving genes encoding the CLRs Dectin-1, Dectin-2 and Mincle. Genetic deletion of these individual CLRs revealed an essential role for Mincle. Mincle activation was sufficient to generate the EAU phenotype, and this required activation of both Syk and Card9. In contrast, Dectin-1 contributed minimally and a possible repressive role was shown for Dectin-2. These findings extend our understanding of CLRs in autoimmune uveitis. The newly identified role of Mincle and Syk/Card9-coupled signaling axis in autoimmune uveitis could provide novel targets for treatment of patients with ocular inflammatory disease.

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Section: Discussionmentioning

confidence: 99%

Mincle Activation and the Syk/Card9 Signaling Axis Are Central to the Development of Autoimmune Disease of the Eye

Lee

Brown

Vance

et al. 2016

The Journal of Immunology

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“…Furthermore, β-glucans have been successfully used to enhance antitumor responses, confirming their potential in this capacity 105 . Mycobacterial cord factor appears to be a specific ligand for MINCLE-MCL and has successfully been used in mice for vaccinations against mycobacterial infections 87,106 . Moreover, viral envelope glycoproteins allow the targeting of several CLRs, such as DC-SIGN, langerin, DC immuno receptor (DCIR; also known as CLEC4A) and mannose receptor, and when used in combination with TLR ligands, these glycoproteins have been shown to modulate innate signalling that shapes immunity 37,54,107 .…”

Section: Harnessing Clrs For Vaccine Designmentioning

confidence: 99%

C-type lectin receptors in the control of T helper cell differentiation

2016

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Pathogen recognition by C-type lectin receptors (CLRs) expressed by dendritic cells is important not only for antigen presentation, but also for the induction of appropriate adaptive immune responses via T helper (TH) cell differentiation. CLRs act either by themselves or in cooperation with other receptors, such as other CLRs, Toll-like receptors and interferon receptors, to induce signalling pathways that trigger specialized cytokine programmes for polarization of TH cell differentiation. In this Review, we discuss how triggering of the prototypical CLRs leads to distinct pathogen-tailored TH cell responses and how we can harness our expanding knowledge for vaccine design and the treatment of inflammatory and malignant diseases.

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“…[32][33][34] All rats were sacriced by luxation of cervical vertebra to collect the same section of the right lung tissue, which was then xed in 10% neutral formalin and embedded in paraffin. Paraffin sections were deparaffinized, rehydrated in xylene and ethanol and then treated with 3% H 2 O 2 (Boster Biological Technology, Ltd, Wuhan, CN) for 10 min to suppress endogenous peroxidase activity and reduce background staining.…”

Section: Immunouorescence (If)mentioning

confidence: 99%

Dendritic cells trigger imbalance of Th1/Th2 cells in silica dust exposure rat model via MHC-II, CD80, CD86 and IL-12

et al. 2018

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Silicosis is one of the most common occupational respiratory diseases caused by inhaling silica dust over a prolonged period of time, and the progression of silicosis is accompanied with chronic inflammation and progressive pulmonary fibrosis, in which dendritic cells (DCs), the most powerful antigen presentation cell (APC) in the immune response, play a crucial role. To investigate the role of DCs in the development of silicosis, we established an experimental silicosis rat model and examined the number of DCs and alveolar macrophages (AMs) in lung tissues using immunofluorescence over 84 days. Additionally, to obtain an overview of the immunological changes in rat lung tissues, a series of indicators including Th1/Th2 cells, IFN-g, IL-4, MHC-II, CD80/86 and IL-12 were detected using flow cytometry and an enzyme-linked immunosorbent assay (ELISA) as well as a real-time polymerase chain reaction (PCR) assay. We observed that the number of DCs slightly increased at the inflammatory stage, and it increased significantly at the final stage of fibrosis. Polarization of Th1 cells and IFN-g expressions were dominant during the inflammatory stage, whereas polarization of Th2 cells and IL-4 expressions were dominant during the fibrotic stage. The subsequent mechanistic study found that the expressions of MHC-II, CD80/86 and IL-12, which are the key molecules that connect DCs and Th cells, changed dynamically in the experimental silicosis rat model. The data obtained in this study indicated that the increase in DCs may contribute to polarization of Th1/Th2 cells via MHC-II, CD80/86, and IL-12 in silica dust-exposed rats.

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Macrophage-Inducible C-Type Lectin Mincle-Expressing Dendritic Cells Contribute to Control of Splenic Mycobacterium bovis BCG Infection in Mice

Cited by 40 publications

References 38 publications

Mincle Activation and the Syk/Card9 Signaling Axis Are Central to the Development of Autoimmune Disease of the Eye

Mincle Activation and the Syk/Card9 Signaling Axis Are Central to the Development of Autoimmune Disease of the Eye

C-type lectin receptors in the control of T helper cell differentiation

Dendritic cells trigger imbalance of Th1/Th2 cells in silica dust exposure rat model via MHC-II, CD80, CD86 and IL-12

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