Transcriptomic signature and metabolic programming of bovine classical and nonclassical monocytes indicate distinct functional specializations

AbstractSimilar to human monocytes, bovine monocytes can be split into CD14+CD16− classical and CD14−CD16+ nonclassical monocytes (cM and ncM, respectively). Here, we present an in-depth analysis of their steady-state transcriptomes, highlighting pronounced functional specializations. Gene transcription indicates that pro-inflammatory and antibacterial processes are associated with cM, while ncM appear to be specialized in regulatory/anti-inflammatory functions and tissue repair, as well as antiviral responses and T-cell immunomodulation. In support of these functional differences, we found that oxidative phosphorylation prevails in ncM, whereas cM are clearly biased towards aerobic glycolysis. Furthermore, bovine monocyte subsets differed in their responsiveness to TLR ligands, supporting an antiviral role of ncM. Taken together, these data clearly indicate a variety of subset-specific functions in cM and ncM that are likely to be transferable to monocyte subsets of other species, including humans.

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Antiviral RNAi response against the insect-specific Agua Salud alphavirus

10.1101/2021.12.20.473494 ◽

2021 ◽

Author(s):

Mine Altinli ◽

Mayke Leggewie ◽

Marlis Badusche ◽

Rashwita Gyanwali ◽

Christina Scherer ◽

...

Keyword(s):

Rnai Pathway ◽

Nucleotide Bias ◽

Knock Out ◽

Antiviral Responses ◽

Ping Pong ◽

Infected Cells ◽

Sirna Pathway ◽

Antiviral Role ◽

Rnai Response

Arboviruses transmitted by mosquitoes are responsible for the death of millions of people each year. In addition to arboviruses, many insect-specific viruses (ISVs) have been discovered in mosquitoes in the last decade. ISVs, in contrast to arboviruses transmitted by mosquitoes to vertebrates, cannot replicate in vertebrate cells even when they are evolutionarily closely related to arboviruses. The alphavirus genus includes many arboviruses, although only a few ISVs have been discovered from this genus so far. Here, we investigate the interactions of a recently isolated insect-specific alphavirus, Agua-Salud alphavirus (ASALV), with its mosquito host. RNAi is one of the essential antiviral responses against arboviruses, although there is little knowledge on the interactions of RNAi with ISVs. Through knock-down of transcripts of the different key RNAi pathway (siRNA, miRNA and piRNA) proteins, we show the antiviral role of Ago2 (siRNA), Ago1 (miRNA), and Piwi4 proteins against ASALV in Aedes aegypti derived cells. ASALV replication increased in Dicer2 and Ago2 knock-out cells, confirming the antiviral role of the siRNA pathway. In infected cells, mainly ASALV-specific siRNAs are produced while piRNAs, with the characteristic nucleotide bias resulting from ping-pong amplification, are only produced in Dicer2 knock-out cells. Taken together, ASALV interactions with the mosquito RNAi response differs from arthropod-borne alphaviruses in some aspects, although they also share some commonalities. Further research is needed to understand whether the identified differences can be generalised to other insect-specific alphaviruses.

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Faculty Opinions recommendation of Cutting edge: critical role of glycolysis in human plasmacytoid dendritic cell antiviral responses.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726109257.793529142 ◽

2017 ◽

Author(s):

Philippe Saas ◽

Sylvain Perruche

Keyword(s):

Dendritic Cell ◽

Plasmacytoid Dendritic Cell ◽

Critical Role ◽

Cutting Edge ◽

Antiviral Responses

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Microglia in Alzheimer’s Disease

Current Alzheimer Research ◽

10.2174/1567205017666200212155234 ◽

2020 ◽

Vol 17 (1) ◽

pp. 29-43 ◽

Cited By ~ 3

Author(s):

Patrick Süß ◽

Johannes C.M. Schlachetzki

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Disorder ◽

Current Knowledge ◽

Imaging Techniques ◽

Amyloid Β ◽

Disease Stage ◽

Disease Modifying Therapy ◽

Transcriptomic Signature

: Alzheimer’s Disease (AD) is the most frequent neurodegenerative disorder. Although proteinaceous aggregates of extracellular Amyloid-β (Aβ) and intracellular hyperphosphorylated microtubule- associated tau have long been identified as characteristic neuropathological hallmarks of AD, a disease- modifying therapy against these targets has not been successful. An emerging concept is that microglia, the innate immune cells of the brain, are major players in AD pathogenesis. Microglia are longlived tissue-resident professional phagocytes that survey and rapidly respond to changes in their microenvironment. Subpopulations of microglia cluster around Aβ plaques and adopt a transcriptomic signature specifically linked to neurodegeneration. A plethora of molecules and pathways associated with microglia function and dysfunction has been identified as important players in mediating neurodegeneration. However, whether microglia exert either beneficial or detrimental effects in AD pathology may depend on the disease stage. : In this review, we summarize the current knowledge about the stage-dependent role of microglia in AD, including recent insights from genetic and gene expression profiling studies as well as novel imaging techniques focusing on microglia in human AD pathology and AD mouse models.

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Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance

Gut ◽

10.1136/gutjnl-2020-321731 ◽

2020 ◽

pp. gutjnl-2020-321731

Author(s):

Dominik Aschenbrenner ◽

Maria Quaranta ◽

Soumya Banerjee ◽

Nicholas Ilott ◽

Joanneke Jansen ◽

...

Keyword(s):

Mononuclear Cells ◽

Personalised Medicine ◽

Mononuclear Phagocytes ◽

Cytokine Network ◽

Peripheral Blood Mononuclear ◽

Transcriptional Signature ◽

Inflammatory Monocytes ◽

Transcriptomic Signature ◽

Inflammatory Bowel

ObjectiveDysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine.DesignWe performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples.ResultsWe characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease.ConclusionOur work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn’s disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23.

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HO-1 Modulates Aerobic Glycolysis through LDH in Prostate Cancer Cells

Antioxidants ◽

10.3390/antiox10060966 ◽

2021 ◽

Vol 10 (6) ◽

pp. 966

Author(s):

Florencia Cascardo ◽

Nicolás Anselmino ◽

Alejandra Páez ◽

Estefanía Labanca ◽

Pablo Sanchis ◽

...

Keyword(s):

Prostate Cancer ◽

Aerobic Glycolysis ◽

Heme Oxygenase 1 ◽

Free Survival ◽

Atp Production ◽

Inflammatory Damage ◽

Extracellular Lactate ◽

Cellular Energetics ◽

Lactate Levels

Prostate cancer (PCa) is the second most diagnosed malignancy and the fifth leading cause of cancer associated death in men worldwide. Dysregulation of cellular energetics has become a hallmark of cancer, evidenced by numerous connections between signaling pathways that include oncoproteins and key metabolic enzymes. We previously showed that heme oxygenase 1 (HO-1), a cellular homeostatic regulator counteracting oxidative and inflammatory damage, exhibits anti-tumoral activity in PCa cells, inhibiting cell proliferation, migration, tumor growth and angiogenesis. The aim of this study was to assess the role of HO-1 on the metabolic signature of PCa. After HO-1 pharmacological induction with hemin, PC3 and C4-2B cells exhibited a significantly impaired cellular metabolic rate, reflected by glucose uptake, ATP production, lactate dehydrogenase (LDH) activity and extracellular lactate levels. Further, we undertook a bioinformatics approach to assess the clinical significance of LDHA, LDHB and HMOX1 in PCa, identifying that high LDHA or low LDHB expression was associated with reduced relapse free survival (RFS). Interestingly, the shortest RFS was observed for PCa patients with low HMOX1 and high LDHA, while an improved prognosis was observed for those with high HMOX1 and LDHB. Thus, HO-1 induction causes a shift in the cellular metabolic profile of PCa, leading to a less aggressive phenotype of the disease.

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ACCELERATED CARDIAC ALLOGRAFT REJECTION AND GRAFT LOSS AMONG CIGARETTE SMOKERS, ROLE OF INFLAMMATION, OXIDATIVE STRESS AND TISSUE REPAIR MOLECULES

Transplantation Journal ◽

10.1097/01.tp.0000331231.80495.3d ◽

2008 ◽

Vol 86 (Supplement) ◽

pp. 525-526

Author(s):

M Mehra ◽

A Khanna ◽

J Xu ◽

C Baquet

Keyword(s):

Oxidative Stress ◽

Allograft Rejection ◽

Tissue Repair ◽

Graft Loss ◽

Cardiac Allograft ◽

Cigarette Smokers ◽

Cardiac Allograft Rejection

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Essential role of IPS-1 in innate immune responses against RNA viruses

Journal of Experimental Medicine ◽

10.1084/jem.20060792 ◽

2006 ◽

Vol 203 (7) ◽

pp. 1795-1803 ◽

Cited By ~ 345

Author(s):

Himanshu Kumar ◽

Taro Kawai ◽

Hiroki Kato ◽

Shintaro Sato ◽

Ken Takahashi ◽

...

Keyword(s):

Rna Viruses ◽

Rna Virus ◽

Critical Role ◽

Nuclear Factor Κb ◽

Type I ◽

Innate Immune Responses ◽

Antiviral Responses ◽

Deficient Mice

IFN-β promoter stimulator (IPS)-1 was recently identified as an adapter for retinoic acid–inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (Mda5), which recognize distinct RNA viruses. Here we show the critical role of IPS-1 in antiviral responses in vivo. IPS-1–deficient mice showed severe defects in both RIG-I– and Mda5-mediated induction of type I interferon and inflammatory cytokines and were susceptible to RNA virus infection. RNA virus–induced interferon regulatory factor-3 and nuclear factor κB activation was also impaired in IPS-1–deficient cells. IPS-1, however, was not essential for the responses to either DNA virus or double-stranded B-DNA. Thus, IPS-1 is the sole adapter in both RIG-I and Mda5 signaling that mediates effective responses against a variety of RNA viruses.

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Antiviral Role of Phenolic Compounds against Dengue Virus: A Review

Biomolecules ◽

10.3390/biom11010011 ◽

2020 ◽

Vol 11 (1) ◽

pp. 11

Author(s):

Vanessa Loaiza-Cano ◽

Laura Milena Monsalve-Escudero ◽

Carlos da Silva Maia Bezerra Filho ◽

Marlen Martinez-Gutierrez ◽

Damião Pergentino de Sousa

Keyword(s):

Phenolic Compounds ◽

Dengue Virus ◽

Biological Activities ◽

Antiviral Effect ◽

Health Concern ◽

Host Proteins ◽

Viral Particles ◽

Antiviral Role ◽

Productive Replication

Phenolic compounds have been related to multiple biological activities, and the antiviral effect of these compounds has been demonstrated in several viral models of public health concern. In this review, we show the antiviral role of phenolic compounds against dengue virus (DENV), the most widespread arbovirus globally that, after its re-emergence, has caused multiple epidemic outbreaks, especially in the last two years. Twenty phenolic compounds with anti-DENV activity are discussed, including the multiple mechanisms of action, such as those directed against viral particles or viral proteins, host proteins or pathways related to the productive replication viral cycle and the spread of the infection.

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Specialized Pro-Resolving Lipid Mediators in Neonatal Cardiovascular Physiology and Diseases

Antioxidants ◽

10.3390/antiox10060933 ◽

2021 ◽

Vol 10 (6) ◽

pp. 933

Author(s):

Andrea Gila-Diaz ◽

Gloria Herranz Carrillo ◽

Pratibha Singh ◽

David Ramiro-Cortijo

Keyword(s):

Tissue Repair ◽

Cardiovascular Health ◽

Critical Role ◽

Potential Effect ◽

Lipid Mediators ◽

Physiological Effects ◽

Therapeutic Approaches ◽

The Impact ◽

Long Chain

Cardiovascular disease remains a leading cause of mortality worldwide. Unresolved inflammation plays a critical role in cardiovascular diseases development. Specialized Pro-Resolving Mediators (SPMs), derived from long chain polyunsaturated fatty acids (LCPUFAs), enhances the host defense, by resolving the inflammation and tissue repair. In addition, SPMs also have anti-inflammatory properties. These physiological effects depend on the availability of LCPUFAs precursors and cellular metabolic balance. Most of the studies have focused on the impact of SPMs in adult cardiovascular health and diseases. In this review, we discuss LCPUFAs metabolism, SPMs, and their potential effect on cardiovascular health and diseases primarily focusing in neonates. A better understanding of the role of these SPMs in cardiovascular health and diseases in neonates could lead to the development of novel therapeutic approaches in cardiovascular dysfunction.

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