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Plant-Based Adjunct Therapy for Tuberculosis
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Lydia Gibango, Anna-Mari Reid, Jonathan L. Seaman, Namrita Lall
TLRs have been identified in both humans (10 TLRs) and mice (12 TLRs). In humans, TLR2 is found on the cell membrane as a surface receptor and dimerizes with TRL1 or TLR6. The heterodimer formed between TLR1 and TLR2 is responsible for detecting triacylated lipopeptides from mycoplasma or gram-negative bacteria. The heterodimer formed between TLR2 and TLR6 could sense diacylated lipopeptides from mycoplasma or gram-positive bacteria (Circelli et al., 2017). TLR3 is a receptor found in the endosome and has the ability to recognize double-stranded RNA (dsRNA). TLR4 recognizes lipopolysaccharide (LPS), a component found in the outer membrane of gram-negative bacteria (Kawai and Akira, 2010). The only TLR4 agonist used as a cancer vaccine adjuvant that is approved is monophosphoryl lipid A (MPL), which has undergone many clinical trials to prove its safety and probability to elicit an immune response (Cluff, 2010). Both TLR7 and TLR8 are endosomal receptors that recognize single-stranded RNA (ssRNA); TLR7, Imiquimod, is the only approved ligand for use in the treatment of precancerous skin lesions (Vacchelli et al., 2012). TLR9 can identify unmethylated CpG dinucleotides of bacterial DNA origin (Kawai and Akira, 2010). TLRs that have had the ability to steer a Th1 elicited immune response include Poly:IC (TLR3), 3-O-desacyl-4’-monophosphoryl lipid A (MPLA: TLR4) or CpG oligonucleotides (TLR9). They have the ability to activate these specific TLRs and induce a downstream IL-12 response, which is important for the activation of a Th1 response (Stewart et al., 2019).
Helicobacter pylori infection
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Diane Bimczok, Anne Müller, Phillip D. Smith
In contrast, H. pylori recognition involves TLR2 activation. TLR2 is an important surface-expressed PRR that collaborates with TLR1, TLR6, TLR10, and other receptors to recognize bacterial and fungal products. An array of H. pylori-derived molecules, including LPS, heat shock protein 60 (HP-HSP60), and HP-NAP, induce TLR2 activation. Activation of TLR2 leads to NF-κB signaling and induction of cytokine expression by epithelial cells, as well as macrophages, DCs, neutrophils, and B cells. In addition, TLR2 engagement by H. pylori leads to activation of the inflammasome pathway through the Nod-like receptor family member NLRP3, which in turn causes activation of IL-1β, a key pro-inflammatory mediator. H. pylori also signals through TLR9, an intracellular PRR activated by bacterial DNA that can activate both pro-inflammatory and anti-inflammatory pathways. Interestingly, H. pylori DNA is delivered to the intracellular TLR9 through the T4SS encoded by the cag pathogenicity island, through a similar pathway that delivers H. pylori peptidoglycan to NOD1.
Landscape of Papillomavirus in Human Cancers
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Susri Ray Chaudhuri (Guha), Anirban Roy, Indranil Chatterjee, Rahul Roy Chowdhury, Snehasikta Swarnakar
Eukaryotic cells express germ line-encoded receptors of the innate immune system, pathogen recognition receptors (PRRs) that recognize invariant molecular motifs known as pathogen-associated molecular patterns (PAMPs) (Medzhitov and Janeway 1997). Genital tract keratinocytes express several toll-like receptors (TLRs) located either on the cell surface (TLR1, TLR2, TLR4, TLR5, and TLR6) or in the endosome (TLR3 and TLR9) (Nasu and Narahara 2010). TLR7 expression is induced on keratinocytes by triggering TLR3 with double-stranded RNA, a feature of viral infections, thus activating IFN-responsive genes (Kalali et al. 2008). Type I IFNs that elicit predominantly Th1-type cytotoxic responses are produced by activation of TLRs on keratinocytes (Miller and Modlin 2007).
SESLA suppresses the activation of macrophages and dendritic cells after Gram-positive bacterial challenge
Published in Immunopharmacology and Immunotoxicology, 2023
Xinru Jiang, Yanwu Xu, Tiannan Xiang, Hanxiao Zhang, Xiaodong Cheng, Xiao-Dong Yang, Hongyi Hu, Xin Jiang, Yuejuan Zheng
Additionally, the KEGG pathway analysis of DEGs showed that 53 pathways were significantly enriched (p < 0.05) (Supplementary Table 3). The top 20 KEGG pathways were shown in Figure 6(B). As one of the PRRs expressed on the cell membrane, Toll-like receptor 2 (TLR2) can form a heterodimer with a similarly shaped partner TLR6. During S. aureus infection, TLR2/6 heterodimer and other intracellular PRRs (e.g. NOD2 or cryopyrin) activate immune cells upon stimulation by the components of bacteria, e.g. PGN or bacterial lipoproteins, which are considered as the main PAMPs to trigger overwhelming inflammation harmful to the host. The extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) pathways and nuclear factor κB (NF-κB) pathways are common intracellular signaling pathways that are activated and lead to subsequent production of IL-6, TNF-α, IL-1β, IL-12, chemokines and IL-10, etc. [27–29]. PGN is a well-known PAMP of G+ bacteria that is mainly recognized by TLR2, NOD2 or cryopyrin in various immune cells, such as monocytes, macrophages and DCs. Therefore, to investigate the molecular regulatory mechanism by which SESLA suppresses the inflammatory response in macrophages during G+ bacterial infections, we examined the role of SESLA in the modulation of MAPK activation after PGN stimulation. As shown in Figure 6(C), the phosphorylated status of ERK, JNK and p38 was measured in primary peritoneal macrophages, and the results showed that SESLA did not affect the activation of these signaling pathways.
The potential interplay between opioid and the toll-like receptor 4 (TLR-4)
Published in Immunopharmacology and Immunotoxicology, 2023
Nasrin Zare, Marjan Pourhadi, Golnaz Vaseghi, Shaghayegh Haghjooy Javanmard
Previous studies indicate the off-target effects of opioids and opioids agonists on TLR-4 [15]. Although opioid receptors are connected selectively to the (−) isomers of opioids, TLRs can be bound to both (+) and (−) isomers of opioid ligand [9,15]. Thus, TLR-4 plays a critical role in the transmission and retention of chronic pain [2]. Some findings have known several transmembrane molecules that help TLR signaling pathways. TLRs-4 are dimerized with the co-receptors CD14, a glycophosphatidyl inositol-anchored protein, and myeloid differentiation factor 2 (MD2) and then result in pro-inflammatory mediator production [16,17]. Ligand recognition contributes to the assembly of TLR-4/TLR6 heterodimers and induces the production of inflammatory cytokines and ROS [18,19]. These findings suggest that opioids affect TLR-4 signaling. The TLR-4 signaling leads to the undesirable effects of opioids which are used to relieve acute and chronic pain states. The purpose of the current study is to review all the published related papers regarding the potential interplay between opioids and TLRs. The characteristics of selected studies are presented in Table 1.
ZnO nanoparticles: recent advances in ecotoxicity and risk assessment
Published in Drug and Chemical Toxicology, 2020
Jia Du, Junhong Tang, Shaodan Xu, Jingyuan Ge, Yuwei Dong, Huanxuan Li, Meiqing Jin
Macrophages play an essential role in the in vitro toxicology study of nano-ZnO. It was reported that murine macrophages (RAW-264.7) were used to evaluate the cellular association, cytotoxic reaction and inflammatory effect of nano-ZnO (Heng et al.2011). Chang et al. (2013) demonstrated that proinflammatory genes were significantly upregulated in mouse macrophages (RAW-264.7) that were treated with nano-ZnO. These inflammatory responses could lead to the impairment of immune function and sometimes ultimately lead to the death of immune cells (Chang et al.2013). Roy et al. (2014) demonstrated that the expression of activation and maturation markers (CD1d, MHC-II, CD86 and CD71) was enhanced in nano-ZnO-activated macrophages. It was also found that the inflammatory responses caused by nano-ZnO-activated macrophages strongly depended on toll-like receptor (TLR6-mediated) MAPK signaling (Roy et al.2014). Tuomela et al. (2013) reported that exposing human monocyte-derived macrophages (HMDM) to nano-ZnO resulted in dose-dependent cell death and upregulation of cytotoxicity-related gene expression. In vitro studies showed that nano-ZnO at concentrations of up to 100 μg ml−1 induced a slight increase in intracellular ROS and NF-κB TF expression in mouse macrophages (RAW-264.7). The results indicated that nano-ZnO was nontoxic when the dose was below 100 μg ml−1 (Hong et al.2013).