Deletion of Vitamin C biosynthesis enzyme, Arabino-1, 4-lactone oxidase inLeishmania donovaniresults in increased pro-inflammatory responses from host immune cells

Cardiac wall stress induces local and systemic inflammatory responses that are increasingly recognized as key modulators of extracellular matrix remodeling. Hyaluronic acid interacts with immune cells and mesenchymal cells thereby modulating profibrotic signals. Here we tested the hypothesis that 4-methylumbelliferone (4-MU), an inhibitor of hyaluronic acid synthesis, would attenuate inflammation and extracellular matrix remodeling of pressure-overloaded myocardium in C57BL/6J male mice fed with 4-MU and subjected to TAC (transverse aortic constriction) surgery. Flow cytometry of immune cells showed TAC-induced leukocytosis due to an increase of neutrophils and monocytes. 4-MU strongly attenuated both circulating and cardiac leukocyte numbers 3 days after TAC. In the hearts, 4-MU reduced the number of CCR2 − resident macrophages. At later time points, 4-MU also prevented the infiltration of heart tissue by bone marrow-derived circulating monocytes leading to reduced cardiac macrophage counts even 7 weeks after TAC. The long-term attenuation of macrophage-driven inflammation was associated with less myocardial fibrosis in 4-MU-treated compared with untreated mice. Unexpectedly, 4-MU also reduced the development of left ventricular hypertrophy and increased cardiac output after TAC without affecting blood pressure. The data demonstrate that 4-MU reduces both resident and invading cardiac macrophages and may be a promising agent to alleviate pressure-overload induced myocardial damage.

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Inflammatory Cytokines, Immune Cells, and Organ Interactions in Heart Failure

Frontiers in Physiology ◽

10.3389/fphys.2021.695047 ◽

2021 ◽

Vol 12 ◽

Author(s):

Huihui Li ◽

Chen Chen ◽

Dao Wen Wang

Keyword(s):

Heart Failure ◽

Clinical Trials ◽

Inflammatory Cytokines ◽

Immune Cells ◽

Inflammatory Responses ◽

Therapeutic Targets ◽

Pathophysiological Mechanisms

Despite mounting evidence demonstrating the significance of inflammation in the pathophysiological mechanisms of heart failure (HF), most large clinical trials that target the inflammatory responses in HF yielded neutral or even worsening outcomes. Further in-depth understanding about the roles of inflammation in the pathogenesis of HF is eagerly needed. This review summarizes cytokines, cardiac infiltrating immune cells, and extracardiac organs that orchestrate the complex inflammatory responses in HF and highlights emerging therapeutic targets.

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Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

10.20944/preprints202003.0254.v1 ◽

2020 ◽

Author(s):

Abigail Elliot ◽

Henna Myllymäki ◽

Yi Feng

Keyword(s):

Immune Cells ◽

Cancer Biology ◽

Inflammatory Responses ◽

Live Imaging ◽

Innate Immune ◽

Leukocyte Recruitment ◽

Innate Immune Cells ◽

Neoplastic Cells ◽

Tumour Development ◽

Tumour Initiation

The zebrafish is now an important model organism for cancer biology studies and provides some unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level thus providing novel insights into our understanding of cancer. Here we summarise and discuss available transgenic zebrafish tumour models and what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response toward transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour associated macrophages and neutrophils in mammalian models and present evidence which supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to signals mediating leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

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Hydrolyzed fumonisin B1 induces less inflammatory responses than fumonisin B1 in the co-culture model of porcine intestinal epithelial and immune cells

Toxicology Letters ◽

10.1016/j.toxlet.2019.01.013 ◽

2019 ◽

Vol 305 ◽

pp. 110-116 ◽

Cited By ~ 13

Author(s):

Min Jeong Gu ◽

Seung Eun Han ◽

Kyoryen Hwang ◽

Elisabeth Mayer ◽

Nicole Reisinger ◽

...

Keyword(s):

Immune Cells ◽

Inflammatory Responses ◽

Fumonisin B1 ◽

Intestinal Epithelial ◽

Culture Model ◽

Hydrolyzed Fumonisin

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Chemokine receptor trafficking coordinates neutrophil clustering and dispersal at wounds in zebrafish

Nature Communications ◽

10.1038/s41467-019-13107-3 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 9

Author(s):

Caroline Coombs ◽

Antonios Georgantzoglou ◽

Hazel A. Walker ◽

Julian Patt ◽

Nicole Merten ◽

...

Keyword(s):

Plasma Membrane ◽

Chemokine Receptor ◽

Immune Cells ◽

Tissue Damage ◽

Chemokine Receptors ◽

Inflammatory Responses ◽

Receptor Trafficking ◽

Migratory Response ◽

Cell Behaviors ◽

Downstream Signaling

AbstractImmune cells congregate at specific loci to fight infections during inflammatory responses, a process that must be transient and self-resolving. Cell dispersal promotes resolution, but it remains unclear how transition from clustering to dispersal is regulated. Here we show, using quantitative live imaging in zebrafish, that differential ligand-induced trafficking of chemokine receptors such as Cxcr1 and Cxcr2 orchestrates the state of neutrophil congregation at sites of tissue damage. Through receptor mutagenesis and biosensors, we show that Cxcr1 promotes clustering at wound sites, but is promptly desensitized and internalized, which prevents excess congregation. By contrast, Cxcr2 promotes bidirectional motility and is sustained at the plasma membrane. Persistent plasma membrane residence of Cxcr2 prolongs downstream signaling and is required for sustained exploratory motion conducive to dispersal. Thus, differential trafficking of two chemokine receptors allows coordination of antagonistic cell behaviors, promoting a self-resolving migratory response.

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Rumen-bypassed tributyrin alleviates heat stress by reducing the inflammatory responses of immune cells

Poultry Science ◽

10.1016/j.psj.2020.10.006 ◽

2021 ◽

Vol 100 (1) ◽

pp. 348-356

Author(s):

Wenjin Guo ◽

Juxiong Liu ◽

Yuanxi Yang ◽

He Ma ◽

Qian Gong ◽

...

Keyword(s):

Heat Stress ◽

Immune Cells ◽

Inflammatory Responses

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Inflammatory Responses during Tumour Initiation: From Zebrafish Transgenic Models of Cancer to Evidence from Mouse and Man

Cells ◽

10.3390/cells9041018 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1018 ◽

Cited By ~ 1

Author(s):

Abigail Elliot ◽

Henna Myllymäki ◽

Yi Feng

Keyword(s):

Immune Cells ◽

Cancer Biology ◽

Inflammatory Responses ◽

Live Imaging ◽

Innate Immune ◽

Leukocyte Recruitment ◽

Innate Immune Cells ◽

Neoplastic Cells ◽

Tumour Development ◽

Tumour Initiation

The zebrafish is now an important model organism for cancer biology studies and provides unique and complementary opportunities in comparison to the mammalian equivalent. The translucency of zebrafish has allowed in vivo live imaging studies of tumour initiation and progression at the cellular level, providing novel insights into our understanding of cancer. Here we summarise the available transgenic zebrafish tumour models and discuss what we have gleaned from them with respect to cancer inflammation. In particular, we focus on the host inflammatory response towards transformed cells during the pre-neoplastic stage of tumour development. We discuss features of tumour-associated macrophages and neutrophils in mammalian models and present evidence that supports the idea that these inflammatory cells promote early stage tumour development and progression. Direct live imaging of tumour initiation in zebrafish models has shown that the intrinsic inflammation induced by pre-neoplastic cells is tumour promoting. Signals mediating leukocyte recruitment to pre-neoplastic cells in zebrafish correspond to the signals that mediate leukocyte recruitment in mammalian tumours. The activation state of macrophages and neutrophils recruited to pre-neoplastic cells in zebrafish appears to be heterogenous, as seen in mammalian models, which provides an opportunity to study the plasticity of innate immune cells during tumour initiation. Although several potential mechanisms are described that might mediate the trophic function of innate immune cells during tumour initiation in zebrafish, there are several unknowns that are yet to be resolved. Rapid advancement of genetic tools and imaging technologies for zebrafish will facilitate research into the mechanisms that modulate leukocyte function during tumour initiation and identify targets for cancer prevention.

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Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages

Metabolites ◽

10.3390/metabo10090372 ◽

2020 ◽

Vol 10 (9) ◽

pp. 372 ◽

Cited By ~ 2

Author(s):

Karl J. Harber ◽

Kyra E. de Goede ◽

Sanne G. S. Verberk ◽

Elisa Meinster ◽

Helga E. de Vries ◽

...

Keyword(s):

Immune Responses ◽

Immune Cells ◽

Immune Cell ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Cell Phenotype ◽

Independent Manner ◽

Inflammatory Macrophages ◽

Necrosis Factor

Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a lot of attention and emerged as a crucial regulator of macrophage responses and inflammation. Succinate was originally described as a metabolite that supports inflammation via distinct routes. Recently, studies have indicated that succinate and its receptor SUCNR1 can suppress immune responses as well. These apparent contradictory effects might be due to specific experimental settings and particularly the use of distinct succinate forms. We therefore compared the phenotypic and functional effects of distinct succinate forms and receptor mouse models that were previously used for studying succinate immunomodulation. Here, we show that succinate can suppress secretion of inflammatory mediators IL-6, tumor necrosis factor (TNF) and nitric oxide (NO), as well as inhibit Il1b mRNA expression of inflammatory macrophages in a SUCNR1-independent manner. We also observed that macrophage SUCNR1 deficiency led to an enhanced inflammatory response without addition of exogenous succinate. While our study does not reveal new mechanistic insights into how succinate elicits different inflammatory responses, it does indicate that the inflammatory effects of succinate and its receptor SUCNR1 in macrophages are clearly context dependent.

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A Novel Combination of Vitamin C, Curcumin and Glycyrrhizic Acid Potentially Regulates Immune and Inflammatory Response Associated with Coronavirus Infections: A Perspective from System Biology Analysis

Nutrients ◽

10.3390/nu12041193 ◽

2020 ◽

Vol 12 (4) ◽

pp. 1193 ◽

Cited By ~ 22

Author(s):

Liang Chen ◽

Chun Hu ◽

Molly Hood ◽

Xue Zhang ◽

Lu Zhang ◽

...

Keyword(s):

Immune Response ◽

Vitamin C ◽

Inflammatory Response ◽

Signaling Pathways ◽

System Biology ◽

Glycyrrhizic Acid ◽

Inflammatory Responses ◽

Mapk Signaling ◽

Gene Target

Novel coronaviruses (CoV) have emerged periodically around the world in recent years. The recurrent spreading of CoVs imposes an ongoing threat to global health and the economy. Since no specific therapy for these CoVs is available, any beneficial approach (including nutritional and dietary approach) is worth investigation. Based on recent advances in nutrients and phytonutrients research, a novel combination of vitamin C, curcumin and glycyrrhizic acid (VCG Plus) was developed that has potential against CoV infection. System biology tools were applied to explore the potential of VCG Plus in modulating targets and pathways relevant to immune and inflammation responses. Gene target acquisition, gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment were conducted consecutively along with network analysis. The results show that VCG Plus can act on 88 hub targets which are closely connected and associated with immune and inflammatory responses. Specifically, VCG Plus has the potential to regulate innate immune response by acting on NOD-like and Toll-like signaling pathways to promote interferons production, activate and balance T-cells, and regulate the inflammatory response by inhibiting PI3K/AKT, NF-κB and MAPK signaling pathways. All these biological processes and pathways have been well documented in CoV infections studies. Therefore, our findings suggest that VCG Plus may be helpful in regulating immune response to combat CoV infections and inhibit excessive inflammatory responses to prevent the onset of cytokine storm. However, further in vitro and in vivo experiments are warranted to validate the current findings with system biology tools. Our current approach provides a new strategy in predicting formulation rationale when developing new dietary supplements.

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Sensing of HIV-1 by TLR8 activates human T cells and reverses latency

Nature Communications ◽

10.1038/s41467-019-13837-4 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 8

Author(s):

Hany Zekaria Meås ◽

Markus Haug ◽

Marianne Sandvold Beckwith ◽

Claire Louet ◽

Liv Ryan ◽

...

Keyword(s):

T Cells ◽

Immune Cells ◽

Cd4 T Cells ◽

Vaccine Development ◽

Inflammatory Responses ◽

Cell Receptor ◽

Low Grade ◽

Activation Markers ◽

Adaptive Immune Cells ◽

Hiv 1

AbstractDuring HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure of the viral ssRNA genome to endosomal Toll-like receptors (TLRs). TLRs are instrumental in activating inflammatory responses in innate immune cells, but their function in adaptive immune cells is less well understood. Here we show that synthetic ligands of TLR8 boosted T cell receptor signaling, resulting in increased cytokine production and upregulation of surface activation markers. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation towards Th1 and Th17. In addition, we found that endosomal HIV induced cytokine secretion from CD4+ T cells in a TLR8-specific manner. TLR8 engagement also enhanced HIV-1 replication and potentiated the reversal of latency in patient-derived T cells. The adjuvant TLR8 activity in T cells can contribute to viral dissemination in the lymph node and low-grade inflammation in HIV patients. In addition, it can potentially be exploited for therapeutic targeting and vaccine development.

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