Bronchial Epithelial Cells Induce Alternatively Activated Dendritic Cells Dependent on Glucocorticoid Receptor Signaling

Weitnauer, Michael; Schmidt, Lotte; Leong, Nathalie Ng Kuet; Muenchau, Stephanie; Lasitschka, Felix; Eckstein, Volker; Hübner, Sabine; Tuckermann, Jan; Dalpke, Alexander H.

doi:10.4049/jimmunol.1400446

Cited by 10 publications

(9 citation statements)

References 50 publications

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“…The immature status of DC has been previously suggested to account for the immune dysregulation in C. neoformans -infected mice following TNF-α depletion ( 18 ). However, more recent studies with other antigens and/or pathogens suggest that DC can become either classically or alternatively activated, which then directs the subsequent type of T cell polarization ( 21 , 22 ). Classically activated DC (DC1) show robust production of Th1/Th17-polarizing cytokines along with high surface expression of major histocompatibility complex class II (MHC-II) and costimulatory molecules ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

Eastman

Flaczyk

et al. 2016

mBio

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Anti-tumor necrosis factor alpha (anti-TNF-α) therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN) of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC) in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance.

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Section: Introductionmentioning

confidence: 99%

Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

Eastman

Flaczyk

et al. 2016

mBio

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“…5b). Interestingly, MS4A8A was identified as a protein expressed by tumor-associated macrophages and its expression seemed to be a marker for M2 macrophages [54,78]. Although further studies will be needed to understand the exact function of these proteins, the results presented here suggest that specific MS4A proteins might play distinct roles in infiltrating macrophages and microglia during neuroinflammation.…”

Section: Discussionmentioning

confidence: 73%

“…Interestingly, TREM-1 protein expression in macrophages is associated with amplification of the inflammatory immune response and secretion of proinflammatory cytokines, such as IL-6 [53]. Additionally, while Arg2 seems to have a dual role in both M1 and M2 macrophages, expression of Ms4a8a is related to the induction of M2 macrophages [54]. Furthermore, we found Ly6c2 and Ccr2, both of which are associated with M1 (inflammatory) macrophages, to be highly expressed in infiltrating macrophages ( Fig.…”

Section: Reactive Microglia and Infiltrating Macrophages Have Distincmentioning

confidence: 99%

Differential transcriptional profiles identify microglial- and macrophage-specific gene markers expressed during virus-induced neuroinflammation

DePaula-Silva

Gorbea

Doty

et al. 2019

J Neuroinflammation

108

113

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Background In the healthy central nervous system (CNS), microglia are found in a homeostatic state and peripheral macrophages are absent from the brain. Microglia play key roles in maintaining CNS homeostasis and acting as first responders to infection and inflammation, and peripheral macrophages infiltrate the CNS during neuroinflammation. Due to their distinct origins and functions, discrimination between these cell populations is essential to the comprehension of neuroinflammatory disorders. Studies comparing the gene profiles of microglia and peripheral macrophages, or macrophages in vitro-derived from bone marrow, under non-infectious conditions of the CNS, have revealed valuable microglial-specific genes. However, studies comparing gene profiles between CNS-infiltrating macrophages and microglia, when both are isolated from the CNS during viral-induced neuroinflammation, are lacking. Methods We isolated, via flow cytometry, microglia and infiltrating macrophages from the brains of Theiler’s murine encephalomyelitis virus-infected C57BL/6 J mice and used RNA-Seq, followed by validation with qPCR, to examine the differential transcriptional profiles of these cells. We utilized primary literature defining subcellular localization to determine whether or not particular proteins extracted from the transcriptional profiles were expressed at the cell surface. The surface expression and cellular specificity of triggering receptor expressed on myeloid cells 1 (TREM-1) protein were examined via flow cytometry. We also examined the immune response gene profile within the transcriptional profiles of these isolated microglia and infiltrating macrophages. Results We have identified and validated new microglial- and macrophage-specific genes, encoding cell surface proteins, expressed at the peak of neuroinflammation. TREM-1 protein was confirmed to be expressed by infiltrating macrophages, not microglia, at the peak of neuroinflammation. We also identified both unique and redundant immune functions, through examination of the immune response gene profiles, of microglia and infiltrating macrophages during neurotropic viral infection. Conclusions The differential expression of cell surface-specific genes during neuroinflammation can potentially be used to discriminate between microglia and macrophages as well as provide a resource that can be further utilized to target and manipulate specific cell responses during neuroinflammation. Electronic supplementary material The online version of this article (10.1186/s12974-019-1545-x) contains supplementary material, which is available to authorized users.

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“…The tracheal epithelial cells have been found to regulate the gene expression in BMDCs ( 39 ), but whether these respiratory epithelial cell could modulate the long-non coding RNA expression is unclear. To contact the DCs with alveolar epithelial cells (MLE-12), MLE-12 cells were cultured on top of inverted filter inserts.…”

Section: Resultsmentioning

confidence: 99%

lncRNA Malat1 modulates the maturation process, cytokine secretion and apoptosis in airway epithelial cell‑conditioned dendritic cells

Zhang

et al. 2018

Exp Ther Med

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Airway epithelial cells (AECs) are the first point of contact with airborne antigens and are able to instruct resident immune cells to appropriate immune responses. Previous studies have shown that the abnormal expression of metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was associated with tumorigenesis, progression, metastasis, and apoptosis in many cancer types. However, little is known about its functional involvement in the cross-talk of AECs with dendritic cells (DCs). The aim of the present study was to identify Malat1 as a novel epithelial cell-derived immune-modulating factor that contributes to the specific inflammatory-immune airway microenvironment. By using an in vitro co-culture model, where layers of AECs can interact with DCs, and transfecting Malat1 siRNA in AECs, AEC-conditioned DCs were harvested for further analysis of the celluar phenotype, secretion of inflammatory chemokines, and expression of apoptotic markers. The present study clearly demonstrated that Malat1 modulates the maturation process, pro-inflammatory cytokine secretion and apoptosis in AECs-conditioned DCs.

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Bronchial Epithelial Cells Induce Alternatively Activated Dendritic Cells Dependent on Glucocorticoid Receptor Signaling

Cited by 10 publications

References 50 publications

Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

Differential transcriptional profiles identify microglial- and macrophage-specific gene markers expressed during virus-induced neuroinflammation

lncRNA Malat1 modulates the maturation process, cytokine secretion and apoptosis in airway epithelial cell‑conditioned dendritic cells

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