China 
Africa 
Explore chapters and articles related to this topic
Host Response to Biomaterials
Published in Claudio Migliaresi, Antonella Motta, Scaffolds for Tissue Engineering, 2014
Sangeetha Srinivasan, Julia E. Babensee
TLRs are expressed on various cell types including DCs, MOs, T-cells, B-cells, fibroblasts, and ECs.56 TLRs have the ability to specifically recognize pathogen components or pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), teichoic acids, lipoprotein, "double stranded" RNA (dsRNA), bacterial DNA, and flagellin.11'56,64 TLRs 1, 2, 4, 5, and 6 are expressed on the cell surface, while TLRs 3, 7, 8, and 9 are expressed on intracellular compartments, these receptors facilitate the internalization of antigen and trigger subsequent cellular responses.56 Crucial endogenous ligands of TLRs known as damage-associated molecular patterns (DAMPs) or "danger signals" initiate inflammatory responses upon cell death or tissue damage and act as natural adjuvants. Important DAMPs are endogenous molecules that are normally "hidden self" and released upon cell damage or tissue death such as high-mobility group box protein-1 (HMGB1), heat-shock proteins, and mRNA; or upon tissue damage such as heparan sulfate and fibrinogen.49 The ligation of intracellular TLRs leads to the downstream signaling of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and mitogen-activated protein kinase activation via a MyD88-dependent pathway.56,65 TLRs 3 and 4 can activate the transcription factor IFN regulating factor 3 in a MyD88-independent manner. This results in the generation of IFN-b and IFN-inducible gene products.66 NF-kB, also, participates in gene regulation in the MyD88-independent pathway of TLR signaling.11
Macrophage Targeting: A Promising Strategy for Delivery of Chemotherapeutics in Leishmaniasis and Other Visceral Diseases
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Jaya Gopal Meher, Pankaj K. Singh, Yuvraj Singh, Mohini Chaurasia, Anita Singh, Manish K. Chourasia
TLRs, a major class of proteins, also known as immune receptors are a very crucial and abundantly found receptors in immune cells including macrophages. There are 12 TLRs identified in mammals and amongst them TLRs 1–9 are conserved in human beings. Further, these TLRs are located at both extracellular (TLRs–1,–2,–4,–5,–6 and −11) and intracellular (TLRs–3,–7,–8,–9 and −13) regions of the cells and are able to recognize the pathogens at the outer cellular surface or even in the endosomal compartment. After recognizing pathogens, TLRs recruit adaptor proteins (MyD88 or TRIF) and consequently lead to a cascade of cellular events that cause phagocytosis. There are a number of ligands for the TLRs viz. triacyl lipopeptides, LPS, lipoproteins, profilin, alginate, chitosan, and many more that can be employed to target TLRs (Singh et al., 2012). The TLRs have been explored for vaccine delivery and immunotherapy against leishmaniasis. Raman et al. have developed an immunotherapeutic by employing the TLRs-synergy concept for improved immuno-response against cutaneous leishmaniasis. They have selected leishmania poly-protein vaccine (L110f) and combined with TLR4 agonist (monophosphoryl lipid A), and/or TLR9 agonist (CpG) and evaluated them against leishmaniasis. Researchers observed in their in vivo studies that a combination of three performed best against cutaneous leishmaniasis by boosting T cells, reducing parasite burden as well as lesions (Raman et al., 2010). Heuking et al. have worked on development of DNA vaccines for tuberculosis by using TLR2 agonist. They have employed chitosan polymer as a mucoadhesive material and complexed it with TLR2 agonist and plasmid DNA that can act in multiple way by imparting muco-adhesion for enhanced mucosal delivery as well as protection of DNA from degradative factors (Heuking et al., 2009).
PM2.5 aggravates airway inflammation in asthmatic mice: activating NF-κB via MyD88 signaling pathway
Published in International Journal of Environmental Health Research, 2023
Lei Wang, Yanzhi Cui, Hu Liu, Jing Wu, Jie Li, Xiansheng Liu
The study showed that PM2.5 promoted the inflammatory response of MyD88 -/- mice less than that of TLR2 -/- and TLR4 -/- mice. This finding was obtained possibly because the MyD88 pathway is the downstream of all TLR signals, except TLR3 (Takeda and Akira 2015). MyD88 activated IL-1 R-related kinase (IRAK-1 and IRAK-4), and TNF receptor related factor-6 (TRAF-6) (Jefferies et al. 2001). Protein recruitment activated complexes have a wide range, including TGF-β-activated kinase 1 (TAK1), TAB1 (TAK1 binding protein-1), TAB2 and TAB3. TAK1/TAB complex leads to the activation of NF-κB and MAPK signaling pathways (Ruscher et al. 2017). These steps lead to the inflammatory factors expression and inflammatory cells proliferation.
Agrochemical-mediated cardiotoxicity in zebrafish embryos/larvae: What we do and where we go
Published in Critical Reviews in Environmental Science and Technology, 2023
Yang Yang, Yue Tao, Zixu Li, Yunhe Cui, Jinzhu Zhang, Ying Zhang
The immune system mitigates the multiple negative effects of adverse factors by initiating an inflammatory response. In the immune system, macrophages and neutrophils involved in the inflammatory response are recruited to specific sites by chemokines released by mast cells and drive the production of various inflammatory mediators (Belo et al., 2021). Although the inflammatory response is a powerful means of coping with negative effects, continuation of this process or excessive release of inflammatory mediators can lead to tissue damage and even mediate a variety of systemic diseases (Martínez-Navarro et al., 2020). The inflammatory response is closely associated with organ damage in the heart, liver and brain, causing accumulation of macrophages or neutrophils in zebrafish embryos/larvae and increasing ROS levels and the expression of inflammation-related genes (Xie et al., 2021). In the study by Park, Yun, et al. (2021) herbicide dinitramide (6.4 mg L−1, 96 h) mediated the inflammatory response by upregulating the expression levels of inflammation-related genes, which disrupted not only the activity of cardiac development factors, but also the generation of vascular networks. Moreover, the occurrence of inflammatory responses such as abnormal aggregation of inflammatory cells or upregulation of the expression levels of related inflammatory genes was observed in different tissues (liver, heart or brain) of zebrafish after agrochemical stresses such as oxyfluorfen, fenobucarb, naphthalene and paraquat (Chen et al., 2018; Li et al., 2022; Liu et al., 2018; Zhu et al., 2020). Although the inflammatory response in the heart has not been extensively examined, it is evident that the inflammatory response plays an essential role in biotoxicity induction by agrochemicals. Both the accumulation of inflammatory cells, and activation of the nuclear factor (NF)-κB signaling pathway and Toll-like receptor signaling pathway can regulate the level of inflammatory cytokines in zebrafish. Under normal conditions, heterodimeric NF-κB (p65/p50) forms a stable complex with the inhibitory protein IκBα in the cytoplasm. IKKs are activated when extracellular related factors (TNFα and IL-1β) bind to their corresponding receptors (TNF-R1 and IL-1R) on the cell membrane, resulting in phosphorylation and degradation of IκBα, and ultimately leading to translocation of the NF-κB subunit to the nucleus to further mediate inflammatory responses (Pradhan et al., 2012). Moreover, Toll-like receptors that recognize biogenic inflammatory factors such as lipopolysaccharides, peptidoglycans and viral double-stranded RNAs can rapidly activate NF-κB and lead to the production of pro-inflammatory cytokines by activating IKKs via a MyD88-dependent pathway (Lin et al., 2020). Agrochemicals lead to the production of a variety of inflammatory mediators by disrupting the antimicrobial activity of organisms and immune function, suggesting that activation of relevant signaling pathways following agrochemical exposure is attributable to the resurgence of pathogenic microorganisms (Costa et al., 2020).