scholarly journals Length of dsRNA (poly I:C) drives distinct innate immune responses, depending on the cell type

2013 ◽  
Vol 94 (5) ◽  
pp. 1025-1036 ◽  
Author(s):  
M. Firoz Mian ◽  
Amna N. Ahmed ◽  
Mehrnaz Rad ◽  
Artem Babaian ◽  
Dawn Bowdish ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Poly I:C ◽  
Innate Immune Responses ◽  
Cell Type

scholarly journals An In Vitro Assessment of Immunostimulatory Responses to Ten Model Innate Immune Response Modulating Impurities (IIRMIs) and Peptide Drug Product, Teriparatide

Molecules ◽  
2021 ◽  
Vol 26 (24) ◽  
pp. 7461
Author(s):  
Claire K. Holley ◽  
Edward Cedrone ◽  
Duncan Donohue ◽  
Barry W. Neun ◽  
Daniela Verthelyi ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Cytokine Secretion ◽  
Poly I:C ◽  
In Vitro Assays ◽  
Innate Immune Responses ◽  
Vitro Assay

Understanding, predicting, and minimizing the immunogenicity of peptide-based therapeutics are of paramount importance for ensuring the safety and efficacy of these products. The so-called anti-drug antibodies (ADA) may have various clinical consequences, including but not limited to the alteration in the product’s distribution, biological activity, and clearance profiles. The immunogenicity of biotherapeutics can be influenced by immunostimulation triggered by the presence of innate immune response modulating impurities (IIRMIs) inadvertently introduced during the manufacturing process. Herein, we evaluate the applicability of several in vitro assays (i.e., complement activation, leukocyte proliferation, and cytokine secretion) for the screening of innate immune responses induced by ten common IIRMIs (Bacillus subtilis flagellin, FSL-1, zymosan, ODN2006, poly(I:C) HMW, poly(I:C) LMW, CLO75, MDP, ODN2216, and Escherichia coli O111:B4 LPS), and a model biotherapeutic Forteo™ (teriparatide). Our study identifies cytokine secretion from healthy human donor peripheral blood mononuclear cells (PBMC) as a sensitive method for the in vitro monitoring of innate immune responses to individual IIRMIs and teriparatide (TP). We identify signature cytokines, evaluate both broad and narrow multiplex cytokine panels, and discuss how the assay logistics influence the performance of this in vitro assay.

scholarly journals Nanomaterial Exposure Induced Neutrophil Extracellular Traps: A New Target in Inflammation and Innate Immunity

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Hang Yang ◽  
Tony N. Marion ◽  
Yi Liu ◽  
Lingshu Zhang ◽  
Xue Cao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Immune Responses ◽  
Myeloid Cell ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Cell Type ◽  
Extracellular Traps ◽  
Pharmaceutical Industries ◽  
The Relationship

Nanotechnology has become a novel subject with impact in many research and technology areas. Nanoparticles (NPs), as a key component in nanotechnology, are widely used in many areas such as optical, magnetic, electrical, and mechanical engineering. The biomedical and pharmaceutical industries have embraced NPs as a viable drug delivery modality. As such, the potential for NP-induced cytotoxicity has emerged as a major concern for NP drug delivery systems. Thus, it is important to understand how NPs affect the innate immune system. As the most abundant myeloid cell type in innate immune responses, neutrophils are critical for concerns about potentially toxic side effects of NPs. When activated by innate immune stimuli, neutrophils may initiate NETosis to release neutrophil extracellular traps (NETs). Herein, we have reviewed the relationship between NPs and the induction of NETosis and release of NETs.

scholarly journals TANK-binding kinase 1-dependent or -independent signaling elicits the cell-type-specific innate immune responses induced by the adenovirus vector

2015 ◽  
Vol 28 (3) ◽  
pp. 105-115 ◽  
Author(s):  
Sayaka Tsuzuki ◽  
Masashi Tachibana ◽  
Masahisa Hemmi ◽  
Tomoko Yamaguchi ◽  
Masaki Shoji ◽  
...  
Keyword(s):  
Immune Responses ◽  
Adenovirus Vector ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Cell Type ◽  
Cell Type Specific

TLR3 activation stimulates cytokine secretion without altering agonist-induced human small airway contraction or relaxation

2009 ◽  
Vol 297 (3) ◽  
pp. L530-L537 ◽  
Author(s):  
Philip R. Cooper ◽  
Roberta Lamb ◽  
Nicole D. Day ◽  
Patrick J. Branigan ◽  
Radhika Kajekar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Human Lung ◽  
Small Airway ◽  
Innate Immune ◽  
Cytokine Secretion ◽  
Poly I:C ◽  
Innate Immune Responses ◽  
Healthy Human ◽  
Chronic Lung Diseases ◽  
Polycytidylic Acid

Respiratory infections exacerbate chronic lung diseases promoting airway inflammation and hyperreactivity. Toll-like receptor 3 (TLR3) recognizes viral double-stranded (ds) RNA such as polyinosinic-polycytidylic acid [poly(I:C)] and stimulates innate immune responses. The objective of this study was to test the hypothesis that dsRNA promotes lung inflammation and alters airway responsiveness to cholinergic and β-adrenergic receptor agonists in human lung slices. Human airway smooth muscle (ASM) was incubated for 24 h in poly(I:C) ± TNFα and a TLR3 monoclonal antibody. Precision-cut lung slices (PCLS; 250-μm thickness) from healthy human lungs containing a small airway were incubated in 0, 10, or 100 μg/ml poly(I:C) for 24 h. Intravital microscopy of lung slices was used to quantify contractile and relaxation responsiveness to carbachol and isoproterenol, respectively. Supernatants of ASM and PCLS were analyzed for cytokine secretion using a 25-multiplex bead assay. In human ASM, poly(I:C) (0.5 μg/ml) increased macrophage inflammatory protein-1α (MIP-1α) and RANTES that was prevented by a TLR3 monoclonal receptor antibody. Incubation of human PCLS with poly(I:C) (10 and 100 μg/ml) had little effect on the log EC50 or maximum drug effect (Emax) for contraction and relaxation in response to carbachol and isoproterenol, respectively. The responsiveness of the same human PCLS to poly(I:C) incubation was confirmed by the robust increase in chemokines and cytokines. In separate experiments, incubation of PCLS with IL-13 or TNFα (100 ng/ml) increased airway sensitivity to carbachol. Poly(I:C) promotes inflammatory mediator release that was not associated with enhanced bronchoconstriction or attenuated bronchodilation in normal healthy human lung slices. Transduction at the TLR3 initiated by dsRNA stimulates downstream innate immune responses.

scholarly journals Altered Innate Immune Responses in Neutrophils from Patients with Well- and Suboptimally Controlled Asthma

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Francesca S. M. Tang ◽  
Gloria J. Foxley ◽  
Peter G. Gibson ◽  
Janette K. Burgess ◽  
Katherine J. Baines ◽  
...  
Keyword(s):  
Immune Responses ◽  
Respiratory Infections ◽  
Symptom Control ◽  
Innate Immune ◽  
Airflow Limitation ◽  
Poly I:C ◽  
Innate Immune Responses ◽  
Asthma Exacerbations ◽  
Blood Neutrophils ◽  
Refractory Asthma

Background. Respiratory infections are a major cause of asthma exacerbations where neutrophilic inflammation dominates and is associated with steroid refractory asthma. Structural airway cells in asthma differ from nonasthmatics; however it is unknown if neutrophils differ. We investigated neutrophil immune responses in patients who have good (AGood) and suboptimal (ASubopt) asthma symptom control.Methods. Peripheral blood neutrophils fromAGood(ACQ < 0.75,n=11),ASubopt(ACQ > 0.75,n=7), and healthy controls (HC) (n=9) were stimulated with bacterial (LPS (1 μg/mL), fMLF (100 nM)), and viral (imiquimod (3 μg/mL), R848 (1.5 μg/mL), and poly I:C (10 μg/mL)) surrogates or live rhinovirus (RV) 16 (MOI1). Cell-free supernatant was collected after 1 h for neutrophil elastase (NE) and matrix metalloproteinase- (MMP-) 9 measurements or after 24 h for CXCL8 release.Results. Constitutive NE was enhanced inAGoodneutrophils compared to HC. fMLF stimulated neutrophils fromASuboptbut notAGoodproduced 50% of HC levels. fMLF induced MMP-9 was impaired inASuboptandAGoodcompared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV1and FEV1/FVC.ASuboptandAGoodresponded similarly to other stimuli.Conclusions. Circulating neutrophils are different in asthma; however, this is likely to be related to airflow limitation rather than asthma control.

scholarly journals Toll-like receptor-induced innate immune responses in non-parenchymal liver cells are cell type-specific

Immunology ◽  
2010 ◽  
Vol 129 (3) ◽  
pp. 363-374 ◽  
Author(s):  
Jun Wu ◽  
Zhongji Meng ◽  
Min Jiang ◽  
Ejuan Zhang ◽  
Martin Trippler ◽  
...  
Keyword(s):  
Immune Responses ◽  
Liver Cells ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Cell Type ◽  
Parenchymal Liver ◽  
Cell Type Specific

scholarly journals Innate immune responses through Toll-like receptor 3 require human-antigen-R-mediated Atp6v0d2 mRNA stabilization

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mohd Izwan Bin Zainol ◽  
Takumi Kawasaki ◽  
Warunthorn Monwan ◽  
Motoya Murase ◽  
Takuya Sueyoshi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Poly I:C ◽  
Type I ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Mrna Stabilization ◽  
Human Antigen R ◽  
Polycytidylic Acid ◽  
Endosomal Acidification

AbstractToll-like receptor 3 (TLR3) recognizes double-stranded RNA derived from virus and its synthetic analogue, polyinosinic–polycytidylic acid [poly(I:C)]. Upon poly(I:C) binding, TLR3 activates transcription factors to express inflammatory cytokines and type I interferon. TLR3 is located in the endosomes and its recognition of poly(I:C) and activation of downstream signaling is regulated by endosomal acidification. However, the mechanism of post-transcriptional regulation in TLR3-mediated innate responses remains unclear. Here, we focused on Human antigen R (HuR, also known as ELAVL1) that recognizes and binds to the 3′ untranslated regions (3′UTRs) of target mRNAs, thereby protecting them from mRNA degradation, and found that HuR-deficient murine macrophage cells showed significantly reduced Ifnb1 mRNA expression after poly(I:C) stimulation. HuR-deficient cells also showed a marked reduction in the expression of Atp6v0d2 mRNA, which encodes a subunit of vacuolar-type H+ ATPase (V-ATPase), and therefore reduced endosomal acidification. HuR associated with the 3′UTR of Atp6v0d2 mRNA and the stability of Atp6v0d2 mRNA was maintained by its association with HuR. Taken together, our results suggest that HuR stabilizes Atp6v0d2 mRNA, which is required for the TLR3-mediated innate immune responses.

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