scholarly journals Toll-Like Receptors-2 and -4 in Graves’ Disease—Key Players or Bystanders?

2019 ◽  
Vol 20 (19) ◽  
pp. 4732
Author(s):  
Agnieszka Polak ◽  
Ewelina Grywalska ◽  
Janusz Klatka ◽  
Jacek Roliński ◽  
Beata Matyjaszek-Matuszek ◽  
...  

Graves’ disease (GD) is an autoimmune disease that affects the thyroid. The development of autoimmunity is associated with innate immune responses where the prominent role plays Toll-like receptors (TLRs). The aim of our study was to assess the relationship between the expression levels of TLR-2 and TLR-4 on CD4+ and CD8+ T as well as CD19+ B lymphocytes in patients with GD and selected clinical parameters. The study group consisted of 32 women with GD, the control group consisted of 20 healthy women. Immunophenotyping was performed using the flow cytometry and cytokines concentrations were assessed using ELISA assay. The mean percentage of CD4+/TLR-2+ and CD8+/TLR-2+ T cells in patients with GD was higher than in the control group (p < 0.0001). After obtaining euthyroidism, the mean percentage of CD4+/TLR-2+ T cells in patients with GD decreased (p < 0.0001). The expression level of TLR-2 on CD4+ T lymphocytes correlated with serum FT3 concentration in patients with GD (r = 0.47, p = 0.007). The mean percentage of CD8+/TLR-2+ T cells in patients with GD before treatment compared to patients with GD after obtaining euthyroidism was higher (p = 0.0163). Similar findings were found for TLR-4. Thus the TLR-2 and TLR-4 can be a prognostic marker for Graves’ disease.

2019 ◽  
Vol 116 (50) ◽  
pp. 25106-25114 ◽  
Author(s):  
Wenqian Li ◽  
Jun Yan ◽  
Yan Yu

Receptors of innate immune cells function synergistically to detect pathogens and elicit appropriate immune responses. Many receptor pairs also appear “colocalized” on the membranes of phagosomes, the intracellular compartments for pathogen ingestion. However, the nature of the seemingly receptor colocalization and the role it plays in immune regulation are unclear, due to the inaccessibility of intracellular phagocytic receptors. Here, we report a geometric manipulation technique to directly probe the role of phagocytic receptor “colocalization” in innate immune regulation. Using particles with spatially patterned ligands as phagocytic targets, we can decouple the receptor pair, Dectin-1 and Toll-like receptor (TLR)2, to opposite sides on a single phagosome or bring them into nanoscale proximity without changing the overall membrane composition. We show that Dectin-1 enhances immune responses triggered predominantly by TLR2 when their centroid-to-centroid proximity is <500 nm, but this signaling synergy diminishes upon receptor segregation beyond this threshold distance. Our results demonstrate that nanoscale proximity, not necessarily colocalization, between Dectin-1 and TLR2 is required for their synergistic regulation of macrophage immune responses. This study elucidates the relationship between the spatial organization of phagocytic receptors and innate immune responses. It showcases a technique that allows spatial manipulation of receptors and their signal cross-talk on phagosomes inside living cells.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Hang Yang ◽  
Tony N. Marion ◽  
Yi Liu ◽  
Lingshu Zhang ◽  
Xue Cao ◽  
...  

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.


Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2060
Author(s):  
Yu Zhang ◽  
Shuaiyin Chen ◽  
Yuefei Jin ◽  
Wangquan Ji ◽  
Weiguo Zhang ◽  
...  

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the Coronaviridae family, which is responsible for the COVID-19 pandemic followed by unprecedented global societal and economic disruptive impact. The innate immune system is the body’s first line of defense against invading pathogens and is induced by a variety of cellular receptors that sense viral components. However, various strategies are exploited by SARS-CoV-2 to disrupt the antiviral innate immune responses. Innate immune dysfunction is characterized by the weak generation of type I interferons (IFNs) and the hypersecretion of pro-inflammatory cytokines, leading to mortality and organ injury in patients with COVID-19. This review summarizes the existing understanding of the mutual effects between SARS-CoV-2 and the type I IFN (IFN-α/β) responses, emphasizing the relationship between host innate immune signaling and viral proteases with an insight on tackling potential therapeutic targets.


2016 ◽  
Vol 23 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Mathieu Garand ◽  
Bing Cai ◽  
Tobias R Kollmann

Susceptibility to infection and response to vaccination differ between populations and as a function of age. The underlying mechanisms for this age- and population-dependent variation are not known. Specifically, it is unclear if these variations are due to differences in genetically encoded host programs or driven by environmental influences or a combination of both. To address the relationship between gene and environment regarding immune ontogeny, we determined the innate cytokine responses following PRR stimulation of blood mononuclear cells at birth, 1, and 2 yr of age in infants from Caucasian vs . Asian parents and were raised in the same city. At birth, we found that innate cytokine responses were significantly elevated in Asian compared with Caucasian infants. However, these differences waned and responses became more similar over the course of 1–2 yr of living in a similar environment. Our observations that innate response differences present at birth subsequently equalized rather than diverged suggest a key role for environmental effects common to both racial groups in shaping the innate immune responses early in life. Delineating the underlying environmental factors that modulate innate immune responses early in life could provide avenues for targeted beneficial immune modulation.


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