scholarly journals Immune responses of macrophages and dendritic cells regulated by mTOR signalling

2013 ◽  
Vol 41 (4) ◽  
pp. 927-933 ◽  
Author(s):  
Karl Katholnig ◽  
Monika Linke ◽  
Ha Pham ◽  
Markus Hengstschläger ◽  
Thomas Weichhart
Keyword(s):  
Dendritic Cells ◽  
Immune System ◽  
Immune Responses ◽  
Inflammatory Mediators ◽  
Cellular Response ◽  
Mtor Pathway ◽  
The Body ◽  
Innate Immune ◽  
Immune Functions ◽  
Tissue Remodelling

The innate myeloid immune system is a complex network of cells that protect against disease by identifying and killing pathogens and tumour cells, but it is also implicated in homoeostatic mechanisms such as tissue remodelling and wound healing. Myeloid phagocytes such as monocytes, macrophages or dendritic cells are at the basis of controlling these immune responses in all tissues of the body. In the present review, we summarize recent studies demonstrating that mTOR [mammalian (or mechanistic) target of rapamycin] regulates innate immune reactions in macrophages and dendritic cells. The mTOR pathway serves as a decision maker to control the cellular response to pathogens and tumours by regulating the expression of inflammatory mediators such as cytokines, chemokines or interferons. In addition to various in vivo mouse models, kidney transplant patients under mTOR inhibitor therapy allowed the elucidation of important innate immune functions regulated by mTOR in humans. The role of the mTOR pathway in macrophages and dendritic cells enhances our understanding of the immune system and suggests new therapeutic avenues for the regulation of pro- versus anti-inflammatory mediators with potential relevance to cancer therapy, the design of novel adjuvants and the control of distinct infectious and autoimmune diseases.

scholarly journals Innate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Melanie R. Neeland ◽  
Samantha Bannister ◽  
Vanessa Clifford ◽  
Kate Dohle ◽  
Kim Mulholland ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Acute Phase ◽  
Innate Immune ◽  
Low Density ◽  
Innate Immune Responses ◽  
Immunological Mechanisms ◽  
Activated Neutrophils ◽  
Classical Monocytes

AbstractChildren have mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (COVID-19) compared to adults and the immunological mechanisms underlying this difference remain unclear. Here, we report acute and convalescent innate immune responses in 48 children and 70 adults infected with, or exposed to, SARS-CoV-2. We find clinically mild SARS-CoV-2 infection in children is characterised by reduced circulating subsets of monocytes (classical, intermediate, non-classical), dendritic cells and natural killer cells during the acute phase. In contrast, SARS-CoV-2-infected adults show reduced proportions of non-classical monocytes only. We also observe increased proportions of CD63+ activated neutrophils during the acute phase to SARS-CoV-2 in infected children. Children and adults exposed to SARS-CoV-2 but negative on PCR testing display increased proportions of low-density neutrophils that we observe up to 7 weeks post exposure. This study characterises the innate immune response during SARS-CoV-2 infection and household exposure in children.

Effect of aerobic exercise on innate immune responses and inflammatory mediators in the spinal cord of diabetic rats

2020 ◽  
Vol 16 (4) ◽  
pp. 293-301
Author(s):  
A. Kaki ◽  
M. Nikbakht ◽  
A.H. Habibi ◽  
H.F. Moghadam
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Immune Responses ◽  
Diabetic Neuropathy ◽  
Aerobic Exercise ◽  
Inflammatory Mediators ◽  
Innate Immune ◽  
Moderate Intensity ◽  
Innate Immune Responses ◽  
Tnf Α

Neuronal inflammation is one of the pathophysiological causes of diabetes neuropathic pain. The purpose of this research was to determine the effect of aerobic exercise on innate immune responses and inflammatory mediators in the spinal dorsal horn in rats with diabetic neuropathic pain. 40 eight-week-old male Wistar rats (weight range 220±10.2 g) were randomly divided into four groups of (1) sedentary diabetic neuropathy (SDN), (2) training diabetic neuropathy (TDN), (3) training control (TC), and (4) sedentary control (SC). Diabetes was induced by injection of streptozocin (50 mg/kg). Following confirmation of behavioural tests for diabetes neuropathy, the training groups performed 6 weeks of moderate-intensity aerobic exercise on the treadmill. The expression of Toll like receptor (TLR)4, TLR2, tumour necrosis factor (TNF)-α, interleukin (IL)-1β and IL-10 genes in L4-L6 spinal cord sensory neurons was measured by Real Time PCR. Two-way ANOVA and Bonferroni’s post hoc tests were used for statistical analysis. After performing aerobic exercise protocol, the TDN compared to the SDN showed a significant decrease in the mean score of pain in the formalin test and a significant increase in the latency in Tail-Flick test was observed. The expression of TLR4, TLR2, TNF-α and IL-1β genes was significantly higher in the SDN than in the SC group (P<0.05). The expression of the above genes in the TDN was significantly lower than the SDN group (P<0.05). Also, the expression level of IL-10 gene was significantly higher in the TDN than the SDN group (P<0.05). Aerobic exercise improved sensitivity of nociceptors to pain-inducing agents in diabetic neuropathy due to inhibition of inflammatory receptors and increased levels of anti-inflammatory agents in the nervous system. Thus, aerobic exercise should be used as a non-pharmacological intervention for diabetic patients to reduce neuropathic pain.

scholarly journals Recent insights into the implications of metabolism in plasmacytoid dendritic cell innate functions: Potential ways to control these functions

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 456 ◽  
Author(s):  
Philippe Saas ◽  
Alexis Varin ◽  
Sylvain Perruche ◽  
Adam Ceroi
Keyword(s):  
Dendritic Cells ◽  
Lipid Metabolism ◽  
Nuclear Receptors ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Plasmacytoid Dendritic Cell ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Cells ◽  
Immune Functions

There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β). Through these functions, PDC participate in antimicrobial responses or maintenance of immune tolerance, and have been implicated in the pathophysiology of several autoimmune diseases. Recent data support the idea that the glycolytic pathway (or glycolysis), as well as lipid metabolism (including both cholesterol and fatty acid metabolism) may impact some innate immune functions of PDC or may be involved in these functions after Toll-like receptor (TLR) 7/9 triggering. Some differences may be related to the origin of PDC (human versus mouse PDC or blood-sorted versus FLT3 ligand stimulated-bone marrow-sorted PDC). The kinetics of glycolysis may differ between human and murine PDC. In mouse PDC, metabolism changes promoted by TLR7/9 activation may depend on an autocrine/paracrine loop, implicating type I IFN and its receptor IFNAR, explaining a delayed glycolysis. Moreover, PDC functions can be modulated by the metabolism of cholesterol and fatty acids. This may occur via the production of lipid ligands that activate nuclear receptors (e.g., liver X receptor [LXR]) in PDC or through limiting intracellular cholesterol pool size (by statins or LXR agonists) in these cells. Finally, lipid-activated nuclear receptors (i.e., LXR or peroxisome proliferator activated receptor) may also directly interact with pro-inflammatory transcription factors, such as NF-κB. Here, we discuss how glycolysis and lipid metabolism may modulate PDC functions and how this may be harnessed in pathological situations where PDC play a detrimental role.

scholarly journals Commensal and Opportunistic Bacteria Present in the Microbiota in Atlantic Cod (Gadus morhua) Larvae Differentially Alter the Hosts’ Innate Immune Responses

2021 ◽  
Vol 10 (1) ◽  
pp. 24
Author(s):  
Ragnhild Inderberg Vestrum ◽  
Torunn Forberg ◽  
Birgit Luef ◽  
Ingrid Bakke ◽  
Per Winge ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Atlantic Cod ◽  
Innate Immune ◽  
Rrna Gene ◽  
Innate Immune Responses ◽  
Transcriptional Responses ◽  
Gut Morphology ◽  
Germ Free ◽  
Opportunistic Bacteria

The roles of host-associated bacteria have gained attention lately, and we now recognise that the microbiota is essential in processes such as digestion, development of the immune system and gut function. In this study, Atlantic cod larvae were reared under germ-free, gnotobiotic and conventional conditions. Water and fish microbiota were characterised by 16S rRNA gene analyses. The cod larvae’s transcriptional responses to the different microbial conditions were analysed by a custom Agilent 44 k oligo microarray. Gut development was assessed by transmission electron microscopy (TEM). Water and fish microbiota differed significantly in the conventional treatment and were dominated by different fast-growing bacteria. Our study indicates that components of the innate immune system of cod larvae are downregulated by the presence of non-pathogenic bacteria, and thus may be turned on by default in the early larval stages. We see indications of decreased nutrient uptake in the absence of bacteria. The bacteria also influence the gut morphology, reflected in shorter microvilli with higher density in the conventional larvae than in the germ-free larvae. The fact that the microbiota alters innate immune responses and gut morphology demonstrates its important role in marine larval development.

scholarly journals Mitochondria surveillance systems trigger innate immune responses to bacterial pathogens via AMPK pathway in C. elegans

2020 ◽  
Author(s):  
Shouyong Ju ◽  
Hanqiao Chen ◽  
Shaoying Wang ◽  
Jian Lin ◽  
Raffi V Aroian ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Innate Immune ◽  
Surveillance Systems ◽  
Innate Immune Responses ◽  
Energy Status ◽  
Microbial Infection ◽  
C Elegans ◽  
Host Interaction ◽  
Intracellular Energy

AbstractPathogen recognition and triggering pattern of host innate immune system is critical to understanding pathogen-host interaction. It is generally accepted that the microbial infection can be recognized by host via pattern-triggered immunity (PTI) or effector-triggered immunity (ETI) responses. Recently, non-PRR-mediated cellular surveillance systems have been reported as an important supplement strategy to PTI and ETI responses. However, the mechanism of how surveillance systems sense pathogens and trigger innate immune responses is largely unknown. In the present study, using Bacillus thuringiensis-Caenorhabditis elegans as a model, we found a new approach for surveillance systems to sense the pathogens through no-PPRs patterns. We reported C. elegans can monitor intracellular energy status through the mitochondrial surveillance system to triggered innate immune responses against pathogenic attack via AMP-activated protein kinase (AMPK). Consider that the mitochondria surveillance systems and AMPK are conserved components from worms to mammals, our study suggests that disrupting mitochondrial homeostasis to activate the immune system through AMPK-dependent pathways may widely existing in animals.

scholarly journals Regulation of the Migration of Distinct Dendritic Cell Subsets

2021 ◽  
Vol 9 ◽  
Author(s):  
Meng Feng ◽  
Shuping Zhou ◽  
Yong Yu ◽  
Qinghong Su ◽  
Xiaofan Li ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Immune Responses ◽  
The Body ◽  
Inflammatory Factors ◽  
Pathogenic Microorganisms ◽  
Migration Patterns ◽  
Dendritic Cell Subsets ◽  
And Migration ◽  
Antigen Presenting

Dendritic cells (DCs), a class of antigen-presenting cells, are widely present in tissues and apparatuses of the body, and their ability to migrate is key for the initiation of immune activation and tolerogenic immune responses. The importance of DCs migration for their differentiation, phenotypic states, and immunologic functions has attracted widespread attention. In this review, we discussed and compared the chemokines, membrane molecules, and migration patterns of conventional DCs, plasmocytoid DCs, and recently proposed DC subgroups. We also review the promoters and inhibitors that affect DCs migration, including the hypoxia microenvironment, tumor microenvironment, inflammatory factors, and pathogenic microorganisms. Further understanding of the migration mechanisms and regulatory factors of DC subgroups provides new insights for the treatment of diseases, such as infection, tumors, and vaccine preparation.

scholarly journals The neuropeptide receptor NMUR-1 regulates the specificity of C. elegans innate immunity against pathogen infection

2021 ◽  
Author(s):  
Phillip Wibisono ◽  
Shawndra Wibisono ◽  
Jan Watteyne ◽  
Chia-Hui Chen ◽  
Durai Sellegounder ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Genes ◽  
C Elegans ◽  
Adaptive Immune ◽  
Functional Assays

A key question in current immunology is how the innate immune system generates high levels of specificity. Like most invertebrates, Caenorhabditis elegans does not have an adaptive immune system and relies solely on innate immunity to defend itself against pathogen attacks, yet it can still differentiate different pathogens and launch distinct innate immune responses. Here, we have found that functional loss of NMUR-1, a neuronal GPCR homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans survival against various bacterial pathogens. Transcriptomic analyses and functional assays revealed that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens. Our study has uncovered a molecular basis for the specificity of C. elegans innate immunity that could provide mechanistic insights into understanding the specificity of vertebrate innate immunity.

scholarly journals Innate immunity and the pneumococcus

Microbiology ◽  
2006 ◽  
Vol 152 (2) ◽  
pp. 285-293 ◽  
Author(s):  
Gavin K. Paterson ◽  
Tim J. Mitchell
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Innate Immune System ◽  
Innate Immune ◽  
First Line ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Made In

The innate immune system provides a non-specific first line of defence against microbes and is crucial both in the development and effector stages of subsequent adaptive immune responses. Consistent with its importance, study of the innate immune system is a broad and fast-moving field. Here we provide an overview of the recent key advances made in this area with relation to the important pathogen Streptococcus pneumoniae (the pneumococcus).

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