Unveiling the Long Non-Coding RNA Profile of Porcine Reproductive and Respiratory Syndrome Virus-Infected Porcine Alveolar Macrophages

Abstract BackgroundLong noncoding RNA (lncRNA) is highly associated with inflammatory response and virus-induced interferon production. By far the majority of studies have focused on the immune-related lncRNAs of mice and humans, but the function of lncRNAs in porcine immune cells are poorly understood. Porcine reproductive and respiratory syndrome virus (PRRSV) impairs local immune responses in the lungs of nursery and growing pigs, whereas the virus triggers the inflammatory responses. Porcine alveolar macrophage (PAM) is the primary target cell of PRRSV, thus PRRSV is used as an in vitro model of inflammation. Here, we profiled lncRNA and mRNA repertories from PRRSV-infected PAMs to explore the underlying mechanism of porcine lncRNAs in regulating host immune responses. ResultsIn this study, a total of 474 annotated lncRNAs and 2664 novel lncRNAs in PAMs were identified through RNA-seq analysis. Among them 88 differentially expressed (DE) lncRNAs and 407 DE protein-coding mRNAs were identified upon PRRSV incubation. GO category and KEGG pathway enrichment analyses revealed that these DE lncRNAs and mRNAs were mainly involved in inflammation- and pathogen infection-induced pathways. The results of dynamic correlated expression networks between lncRNAs and their predicted target genes uncovered that numerous lncRNAs, such as XLOC-022175, XLOC-019295, and XLOC-017089, were correlated with innate immune genes. Further analysis validated that these three lncRNAs were positively correlated with their predicted target genes including CXCL2, IFI6, and CD163. This study suggests that porcine lncRNAs affect immune responses against PRRSV infection through regulating their target genes in PAMs. ConclusionThis study provides both transcriptomic and epigenetic status of porcine macrophages. In response to PRRSV infection, comprehensive DE lncRNAs and mRNAs were profiled from PAMs. Co-expression analysis demonstrated that lncRNAs are emerging as the important modulators of immune gene activities through their critical influence upon PRRSV infection in porcine macrophages.

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Unveiling the long non-coding RNA profile of porcine reproductive and respiratory syndrome virus-infected porcine alveolar macrophages

BMC Genomics ◽

10.1186/s12864-021-07482-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Junxin Gao ◽

Yu Pan ◽

Yunfei Xu ◽

Wenli Zhang ◽

Lin Zhang ◽

...

Keyword(s):

Immune Responses ◽

Noncoding Rna ◽

Target Genes ◽

Inflammatory Responses ◽

Underlying Mechanism ◽

Growing Pigs ◽

Respiratory Syndrome Virus ◽

Porcine Alveolar Macrophage ◽

Immune Gene

Abstract Background Long noncoding RNA (lncRNA) is highly associated with inflammatory response and virus-induced interferon production. By far the majority of studies have focused on the immune-related lncRNAs of mice and humans, but the function of lncRNAs in porcine immune cells are poorly understood. Porcine reproductive and respiratory syndrome virus (PRRSV) impairs local immune responses in the lungs of nursery and growing pigs, whereas the virus triggers the inflammatory responses. Porcine alveolar macrophage (PAM) is the primary target cell of PRRSV, thus PRRSV is used as an in vitro model of inflammation. Here, we profiled lncRNA and mRNA repertories from PRRSV-infected PAMs to explore the underlying mechanism of porcine lncRNAs in regulating host immune responses. Results In this study, a total of 350 annotated lncRNAs and 1792 novel lncRNAs in PAMs were identified through RNA-seq analysis. Among them 86 differentially expressed (DE) lncRNAs and 406 DE protein-coding mRNAs were identified upon PRRSV incubation. GO category and KEGG pathway enrichment analyses revealed that these DE lncRNAs and mRNAs were mainly involved in inflammation- and pathogen infection-induced pathways. The results of dynamic correlated expression networks between lncRNAs and their predicted target genes uncovered that numerous lncRNAs, such as XLOC-022175, XLOC-019295, and XLOC-017089, were correlated with innate immune genes. Further analysis validated that these three lncRNAs were positively correlated with their predicted target genes including CXCL2, IFI6, and CD163. This study suggests that porcine lncRNAs affect immune responses against PRRSV infection through regulating their target genes in PAMs. Conclusion This study provides both transcriptomic and epigenetic status of porcine macrophages. In response to PRRSV infection, comprehensive DE lncRNAs and mRNAs were profiled from PAMs. Co-expression analysis demonstrated that lncRNAs are emerging as the important modulators of immune gene activities through their critical influence upon PRRSV infection in porcine macrophages.

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A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability

Oncogene ◽

10.1038/s41388-020-01638-9 ◽

2021 ◽

Author(s):

Pengpeng Zhu ◽

Fang He ◽

Yixuan Hou ◽

Gang Tu ◽

Qiao Li ◽

...

Keyword(s):

Breast Cancer ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Underlying Mechanism ◽

Rapid Expansion ◽

Breast Cancer Patients ◽

Coding Region ◽

Signaling Axis

AbstractThe hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.

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hnRNPA2/B1 Ameliorates LPS-Induced Endothelial Injury through NF-κB Pathway and VE-Cadherin/β-Catenin Signaling Modulation In Vitro

Mediators of Inflammation ◽

10.1155/2020/6458791 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Yi Chen ◽

Dan Tang ◽

Linjie Zhu ◽

Tianjie Yuan ◽

Yingfu Jiao ◽

...

Keyword(s):

Endothelial Cells ◽

Inflammatory Responses ◽

Umbilical Vein ◽

Cell Metabolism ◽

Endothelial Permeability ◽

Underlying Mechanism ◽

Endothelial Injury ◽

Inflammatory Factors ◽

Barrier Dysfunction

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is a protein involved in the regulation of RNA processing, cell metabolism, migration, proliferation, and apoptosis. However, the effect of hnRNPA2/B1 on injured endothelial cells (ECs) remains unclear. We investigated the effect of hnRNPA2/B1 on lipopolysaccharide- (LPS-) induced vascular endothelial injury in human umbilical vein endothelial cells (HUVECs) and the underlying mechanisms. LPS was used to induce EC injury, and the roles of hnRNPA2/B1 in EC barrier dysfunction and inflammatory responses were measured by testing endothelial permeability and the expression of inflammatory factors after the suppression and overexpression of hnRNPA2/B1. To explore the underlying mechanism by which hnRNPA2/B1 regulates endothelial injury, we studied the VE-cadherin/β-catenin pathway and NF-κB activation in HUVECs. The results showed that hnRNPA2/B1 was elevated in LPS-stimulated HUVECs. Moreover, knockdown of hnRNPA2/B1 aggravated endothelial injury by increasing EC permeability and promoting the secretion of the inflammatory cytokines TNF-α, IL-1β, and IL-6. Overexpression of hnRNPA2/B1 can reduce the permeability and inflammatory response of HUVEC stimulated by LPS in vitro, while increasing the expression of VE-Cadherin and β-catenin. Furthermore, the suppression of hnRNPA2/B1 increased the LPS-induced NF-κB activation and reduced the VE-cadherin/β-catenin pathway. Taken together, these results suggest that hnRNPA2/B1 can regulate LPS-induced EC damage through regulating the NF-κB and VE-cadherin/β-catenin pathways.

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Investigation and Identification of let-7a Related Functional Proteins in Gastric Carcinoma by Proteomics

Analytical Cellular Pathology ◽

10.1155/2012/691218 ◽

2012 ◽

Vol 35 (4) ◽

pp. 285-295 ◽

Cited By ~ 5

Author(s):

Yimin Zhu ◽

Xingyuan Xiao ◽

Lairong Dong ◽

Zhiming Liu

Keyword(s):

Gastric Carcinoma ◽

Noncoding Rna ◽

Target Genes ◽

Rho Gtpase ◽

Two Dimensional Gel Electrophoresis ◽

Gastric Carcinoma Cell ◽

Rna Molecules ◽

Small Noncoding Rna

MicroRNAs are small noncoding RNA molecules that control expression of target genes. Our previous studies show that let-7a decreased in gastric carcinoma and that up-regulation of let-7a by gene augmentation inhibited gastric carcinoma cell growth bothin vitroandin vivo, whereas it remains largely unclear as to how let-7a affects tumor growth. In this study, proteins associated with the function of let-7a were detected by high throughout screening. The cell line of SGC-7901 stablely overexpressing let-7a was successfully established by gene cloning. Two-dimensional gel electrophoresis (2-DEy was used to separate the total proteins of SGC-7901/let-7a, SGC-7901/EV and SGC-7901, and PDQuest software was applied to analyze 2-DE images. Ten different protein spots were identified by MALDI-TOF-MS, and they may be the proteins associated with let-7a function. The overexpressed proteins included Antioxidant protein 2, Insulin–like growth factor binding protein 2, Protein disulfide isomerase A2, C-1-tetrahydrofolate synthase, Cyclin-dependent kinase inhibitor1 (CDKN1) and Rho–GTPase activating protein 4. The underexpressed proteins consisted of S-phase kinase-associated protein 2 (Spk2), Platelet membrane glycoprotein, Fibronectin and Cks1 protein. Furthermore, the different expression levels of the partial proteins (CDKN1, Spk2 and Fibronectin) were confirmed by western blot analysis. The data suggest that these differential proteins are involved in a novel let-7a signal pathway and these findings provide the basis to investigate the functional mechanisms of let-7a in gastric carcinoma.

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The -172A>G Polymorphism in ADAM17 Promoter Region Enhances Its Binding to EGR1 and Confers Susceptibility to Sepsis Progression

10.21203/rs.3.rs-73158/v1 ◽

2020 ◽

Author(s):

Yiming Shao ◽

Wenying Zhang ◽

Tian Zhao ◽

Furong Lu ◽

Yuan Hong ◽

...

Keyword(s):

Mouse Model ◽

Promoter Region ◽

Inflammatory Responses ◽

Direct Interaction ◽

Underlying Mechanism ◽

Promoter Polymorphism ◽

Enzyme Linked Immunosorbent Assay ◽

A Disintegrin And Metalloproteinase ◽

Early Growth Response 1

Abstract Background: A disintegrin and metalloproteinase 17 (ADAM17) is a proteolytic cleaving protein with a crucial function in inflammatory responses, especially sepsis. But the clear role of ADAM17 in sepsis and the underlying mechanism remained unknown. In this study, we aim to determine the clinical relevance of the ADAM17 rs12692386 (-172A>G) promoter polymorphism in sepsis progression and to further explore the effect and mechanism of the early growth response 1 (EGR1) /ADAM17 pathway in the inflammatory process following sepsis. Methods: A case-control study with a total of 903 sepsis patients and 1150 controls were enrolled to determine the association of ADAM17 -172A>G polymorphism with sepsis. The transcription factor binding to the promoter region of ADAM17 gene was predicted by bioinformatics analysis and verified by Chromatin Immunoprecipitation (ChIP) and luciferase assays. Quantitative real-time PCR and Western blot were performed to detect EGR1 and ADAM17 expression. Cytokine production was detected by enzyme-linked immunosorbent assay. The effect of EGR1/ADAM17 pathway on sepsis-induced inflammatory responses was evaluated in EGR1-silenced cells and endotoxemia mouse model.Results: Patients with sepsis subtype exhibited significantly lower frequencies of the -172AG/GG genotypes compared to those with severe sepsis (29.3% vs. 45.9%, P=0.0002) or septic shock (29.3% vs. 42.4%, P=0.0032). The frequency of -172G allele in the 28-day non-surviving patients was significantly higher than that in the surviving patients (29.3% vs. 21.8%, P=0.0188). The results of in vitro lipopolysaccharide-stimulated and luciferase assays indicated that the −172 A-to-G variation could functionally upregulate promoter activity and transcription of ADAM17 gene via enhancing the binding affinity of its promoter region with the EGR1. The ChIP assay identified the direct interaction. Further studies demonstrated that the EGR1/ADAM17 intervention could significantly decrease the pro-inflammatory cytokine secretion in vitro and improve the survival and inflammatory response of sepsis mouse model.Conclusions: These results provide evidence that the ADAM17 -172A>G polymorphism can functionally enhance ADAM17 expression and promote sepsis-induced inflammatory responses via the EGR1/ADAM17 pathway, which ultimately promote sepsis progression and poor prognosis.

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Mechanisms Involved in Type II Macrophage Activation and Effector Functions

10.26686/wgtn.16973755 ◽

2021 ◽

Author(s):

◽

Marie Clare Lydia Kharkrang

Keyword(s):

Immune Responses ◽

Inflammatory Responses ◽

Surface Marker ◽

Alternative Activation ◽

Type Ii ◽

Activated Macrophages ◽

Phenotypic Properties ◽

Anti Inflammatory ◽

The Impact

<p>Autoimmunities are extremely difficult to treat and involved in their pathogenesis are pro-inflammatory immune responses redirected against one's own tissues. Studies in our lab have shown macrophages that are induced to become type II macrophages protect against an animal model of MS, experimental autoimmune encephalomyelitis (EAE), with protection due to immune deviation. Another way to deviate immune responses away from inflammation is by infection with the parasitic helminth Schistosoma mansoni, which also protects against EAE. The contribution of type II macrophages in this protection is unknown, as are the mechanisms involved in promoting the phenotype induced by type II activation. This project investigates key mechanisms involved in type II activation, while also elucidating the possible effect of schistosome exposure on the induction of this activation state. Using a validated model of type II activation in vitro, we compared the effects of schistosome immune complexes on various macrophage properties such as cytokine, surface marker and enzymatic profiles. This thesis identified that exposure to schistosome complexes induces a macrophage state with characteristics of two distinct activation states (type II and alternative activation), as well as completely novel characteristics. This activation state shows many phenotypic properties associated with immune regulation, and may have important consequences for understanding mechanisms involved in protection against inflammatory illnesses. We also investigated key mechanisms involved in the anti-inflammatory responses induced by type II activation. Cytokine, chemokine and surface marker profiles of macrophages were assessed in response to type II activation in vitro, with the main emphasis on determining the effects of IL-10 and CD40 on the type II activation phenotype and function. This investigation found that type II activated macrophages depend on low levels of CD40/CD40L signalling to polarise Th2 development, as the expression of receptors for Th2-inducing cytokines are significantly impaired in the absence of this interaction. This suggests an important role for the low but maintained levels of CD40 on type II activated macrophages, in aiding the deviation of immune responses, while maintaining Th2 polarization. We also suggest a suppressive role of CD40/CD40L in IL-10 production, which is a novel find. The requirement of new treatments for MS is escalating as more people are affected each year. The impact of MS on the quality of life is severe and long lasting. Having a greater understanding of the mechanisms involved in deviating pro-inflammatory or anti-inflammatory responses will enable the development of much more effective treatments and therapies in the future.</p>

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Attenuated Negative Feedback in Monocyte-Derived Macrophages From Persons Living With HIV: A Role for IKAROS

Frontiers in Immunology ◽

10.3389/fimmu.2021.785905 ◽

2021 ◽

Vol 12 ◽

Author(s):

Celeste Faia ◽

Karlie Plaisance-Bonstaff ◽

Cecilia Vittori ◽

Dorota Wyczechowska ◽

Adam Lassak ◽

...

Keyword(s):

Immune Responses ◽

Negative Feedback ◽

De Novo ◽

Inflammatory Responses ◽

Undetectable Viral Load ◽

Persons Living With Hiv ◽

Epigenetic Remodeling ◽

Living With Hiv ◽

Pro Inflammatory Cytokines

Persons living with HIV (PLWH) are at higher risk of developing secondary illnesses than their uninfected counterparts, suggestive of a dysfunctional immune system in these individuals. Upon exposure to pathogens, monocytes undergo epigenetic remodeling that results in either a trained or a tolerant phenotype, characterized by hyper-responsiveness or hypo-responsiveness to secondary stimuli, respectively. We utilized CD14+ monocytes from virally suppressed PLWH and healthy controls for in vitro analysis following polarization of these cells toward a pro-inflammatory monocyte-derived macrophage (MDM) phenotype. We found that in PLWH-derived MDMs, pro-inflammatory signals (TNFA, IL6, IL1B, miR-155-5p, and IDO1) dominate over negative feedback signals (NCOR2, GSN, MSC, BIN1, and miR-146a-5p), favoring an abnormally trained phenotype. The mechanism of this reduction in negative feedback involves the attenuated expression of IKZF1, a transcription factor required for de novo synthesis of RELA during LPS-induced inflammatory responses. Furthermore, restoring IKZF1 expression in PLWH-MDMs partially reinstated expression of negative regulators of inflammation and lowered the expression of pro-inflammatory cytokines. Overall, this mechanism may provide a link between dysfunctional immune responses and susceptibility to co-morbidities in PLWH with low or undetectable viral load.

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Helminth infection is associated with dampened cytokine responses to viral and bacterial stimulations in Tsimane hunter-horticulturalists

10.1101/2021.09.29.462428 ◽

2021 ◽

Author(s):

India Schneider-Crease ◽

Aaron D. Blackwell ◽

Thomas S. Kraft ◽

Melissa Emery Thompson ◽

Ivan Maldonado Suarez ◽

...

Keyword(s):

Immune Responses ◽

Inflammatory Responses ◽

Remote Communities ◽

Necrosis Factor Alpha ◽

H1n1 Vaccine ◽

Gm Csf ◽

Th2 Cytokine ◽

Cytokine Responses ◽

Macrophage Colony

AbstractBackgroundSoil-transmitted helminth (STH) infections can catalyze immunological changes that affect the response to subsequent infections, particularly those that elicit strong inflammatory responses. As globalization heightens the risk that remote communities with high STH prevalence will encounter novel pathogens, understanding how STHs shape immune responses to these downstream infections becomes increasingly crucial.MethodologyWe worked with Tsimane forager-horticulturalists in the Bolivian Amazon, where STHs are prevalent. We tested whether STHs and eosinophil levels—most likely indicative of infection in this population—are associated with dampened immune responses to in vitro stimulation with H1N1 and lipopolysaccharide (LPS) antigens. Whole blood samples (n = 179) were treated with H1N1 vaccine and LPS and assayed for 13 cytokines (interferon gamma [INF-γ], interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, Granulocyte-macrophage colony-stimulating factor [GM-CSF], and Tumor necrosis factor-alpha [TNF-α]). We evaluated how STHs and eosinophil levels affected cytokine responses and T helper (Th) 1 and Th2-cytokine suite responses to stimulation.ResultsInfection with Ascaris lumbricoides was significantly (p ≤ 0.05) associated with lower response of some cytokines to H1N1 and LPS in women. Eosinophils were significantly negatively associated with some cytokine responses to H1N1 and LPS, with the strongest effects in women, and associated with a reduced Th1- and Th2-cytokine response to H1N1 and LPS in women and men.Conclusions and implicationsWe find that STHs were associated with dampened cytokine responses to certain viral and bacterial antigens, and suggest that this mitigation of host-induced damage may reduce the incidence of cytokine storms in populations with high STH prevalence.

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Exosomes from LPS-Stimulated hDPSCs Activated the Angiogenic Potential of HUVECs In Vitro

Stem Cells International ◽

10.1155/2021/6685307 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Xiangyu Huang ◽

Wei Qiu ◽

Yuhua Pan ◽

Jianjia Li ◽

Zhao Chen ◽

...

Keyword(s):

Pathway Analysis ◽

Target Genes ◽

Underlying Mechanism ◽

Tube Formation ◽

Endothelial Cell Proliferation ◽

Inflammatory Factor ◽

Angiogenic Potential ◽

Vascular Regeneration ◽

Microrna Sequencing

Background. Exosomes from human dental pulp stem cells (hDPSCs) were indicated to play a positive role in vascular regeneration processes. But the angiogenic capabilities of exosomes from inflammatory hDPSCs and the underlying mechanism remain unknown. In this study, the inflammatory factor lipopolysaccharide (LPS) was used to stimulate hDPSCs, and exosomes were extracted from these hDPSCs. The proangiogenic potential of exosomes was examined, and the underlying mechanism was studied. Method. Exosomes were isolated from hDPSCs with or without LPS stimulation (N-EXO and LPS-EXO) and cocultured with human umbilical vein endothelial cells (HUVECs). The proangiogenic potential of exosomes was evaluated by endothelial cell proliferation, migration, and tube formation abilities in vitro. To investigate the proangiogenic mechanism of LPS-EXO, microRNA sequencing was performed to explore the microRNA profile of N-EXO and LPS-EXO. Gene Ontology (GO) analysis was used to study the functions of the predicted target genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was used to estimate the signaling pathways associated with the inflammation-induced angiogenesis process. Result. Compared to the uptake of N-EXO, uptake of LPS-EXO activated the angiogenic potential of HUVECs by promoting the proliferation, migration, and tube formation abilities in vitro. The mRNA expression levels of vascular endothelial growth factor (VEGF) and kinase-insert domain-containing receptor (KDR) in the LPS-EXO group were significantly higher than those in the N-EXO group. MicroRNA sequencing showed that 10 microRNAs were significantly changed in LPS-EXO. Pathway analysis showed that the genes targeted by differentially expressed microRNAs were involved in multiple angiogenesis-related pathways. Conclusion. This study revealed that exosomes derived from inflammatory hDPSCs possessed better proangiogenic potential in vitro. This is the first time to explore the role of exosomal microRNA from hDPSCs in inflammation-induced angiogenesis. This finding sheds new light on the effect of inflammation-stimulated hDPSCs on tissue regeneration.

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Rewiring PBMC responses to prevent CHIKV infection-specific monocyte subset redistribution and cytokine responses

10.1101/2020.06.04.132340 ◽

2020 ◽

Author(s):

José Alberto Aguilar-Briseño ◽

Mariana Ruiz Silva ◽

Jill Moser ◽

Mindaugas Pauzuolis ◽

Jolanda M. Smit ◽

...

Keyword(s):

Immune Responses ◽

Mononuclear Cells ◽

Inflammatory Responses ◽

Chronic Arthritis ◽

Target Cells ◽

Monocyte Subset ◽

Chikv Infection ◽

Peripheral Blood Mononuclear ◽

Vitro Model

AbstractInfection with the mosquito-borne Chikungunya virus (CHIKV) causes acute or chronic arthritis in humans. Inflammatory responses mediated by monocytes, the primary target cells of CHIKV infection in the blood, are considered to play an important role in CHIKV pathogenesis. A recent study revealed that the acute phase of CHIKV infection is characterized by a monocyte-driven response, with an expansion of the intermediate monocyte (IM) subset. In this study, we adopted a previously established in vitro model of CHIKV infection in peripheral blood mononuclear cells, to elucidate the mechanism and relevance of IM expansion in CHIKV replication and associated inflammatory responses. Our data show that infectious but not replication-incompetent CHIKV increases the frequency of IM and to a lesser extent, non-classical (NM) monocytes while reducing the number of classical monocytes (CM). The increase of IM or NM frequency coincided with the activation of inflammatory response and occurred in the absence of lymphocytes implying that monocyte-derived cues are sufficient to drive this effect. Importantly, priming of monocytes with LPS prevented expansion of IM and NM but had no effect on viral replication. It did however alter CHIKV-induced cytokine signature. Taken together, our data delineate the role of IM in CHIKV infection-specific innate immune responses and provide insight for the development of therapeutic strategies that may focus on rewiring monocyte immune responses to prevent CHIKV-mediated arthralgia and arthritis.

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