Toll-like receptors signaling network in pre-eclampsia: An updated review

Toll-like receptors (TLRs) are innate immune cells receptors. They are expressed on leukocytes, epithelial cells, and more particularly on placental immune cells and chorion trophoblast. Upregulation of innate immune response occurs during normal pregnancy, but its excessive activity is involved in the pathology of pregnancy complications including pregnancy-induced hypertension and pre-eclampsia (PE). The recent studies about the overmuch inflammatory responses and aberrant placentation are associated with increased expression of TLRs in PE patients. This review has tried to focus on the relationship between some activities of TLRs and the risk of preeclampsia development.     

Genetic toolkits of the red alga Pyropia tenera against the three most common diseases in Pyropia farms

Disease outbreaks devastate Pyropia aquaculture farms every year. The three most common and serious diseases are Olpidiopsis‐blight and red‐rot disease caused by oomycete pathogens and green‐spot disease caused by the PyroV1 virus. We hypothesized that a basic genetic profile of molecular defenses will be revealed by comparing and analyzing the genetic response of Pyropia tenera against the above three pathogens. RNAs isolated from infected thalli were hybridized onto an oligochip containing 15,115 primers designed from P. tenera expressed sequence tags (EST)s. Microarray profiles of the three diseases were compared and interpreted together with histochemical observation. Massive amounts of reactive oxygen species accumulated in P. tenera cells exposed to oomycete pathogens. Heat shock genes and serine proteases were the most highly up‐regulated genes in all infection experiments. Genes involved in RNA metabolism, ribosomal proteins and antioxidant metabolism were also highly up‐regulated. Genetic profiles of P. tenera in response to pathogens were most similar between the two biotrophic pathogens, Olpidiopsis pyropiae and PyroV1 virus. A group of plant resistance genes were specifically regulated against each pathogen. Our results suggested that disease response in P. tenera consists of a general constitutive defense and a genetic toolkit against specific pathogens.     

囊状幼虫病病毒侵染对中华蜜蜂营养和免疫反应的影响

【目的】囊状幼虫病病毒(sacbrood virus, SBV)是严重危害中华蜜蜂Apis cerana cerana蜂群健康和种群数量的病原微生物,但其对蜜蜂的致死机制不明。本研究旨在探究SBV对不同发育阶段中华蜜蜂营养代谢和免疫的影响。【方法】分别给中华蜜蜂2日龄幼虫和新羽化成虫饲喂SBV,逐日统计死亡蜜蜂数量,检测病毒对蜜蜂存活的影响;利用qPCR检测中华蜜蜂4日龄幼虫、预蛹以及10和20日龄成虫体内SBV RNA、营养代谢基因(ilp1, ilp2, hex110, hex70b, hex70c和vg)、先天性病毒免疫基因(rel, toll, apidaecin, abaecin, defensin, hymenoptaecin, jra, key和state92e)、细胞凋亡基因(atg7和LOC100577876)和抗RNA病毒基因(dis3和dicer)的表达水平。【结果】 SBV感染显著降低了中华蜜蜂幼虫的存活率,但对成虫的生存影响不明显。SBV RNA在中华蜜蜂4日龄幼虫和预蛹体内的表达量显著高于其在10和20日龄成虫体内的表达量。SBV显著降低了中华蜜蜂幼虫营养代谢基因ilp1, ilp2, hex110, hex70b和hex70c以及成虫营养代谢基因vg和hex110的表达量,但显著提高了4日龄幼虫rel, toll, apidaecin, abaecin, defensin, hymenoptaecin和jra以及成虫key和 state92e等先天性病毒免疫基因的表达量,还引起预蛹体内的细胞凋亡基因atg7和LOC100577876的表达量显著增加。【结论】SBV在中华蜜蜂幼虫和预蛹体内的感染水平远高于在成虫体内的,其对幼虫的危害也大于对成虫。SBV显著影响了中华蜜蜂正常的营养代谢,染毒中华蜜蜂能够提高自身的免疫水平来应对;预蛹期中华蜜蜂幼虫细胞凋亡水平的显著增加可能与化蛹异常及死亡有关。     

Nod1-mediated lipolysis promotes diacylglycerol accumulation and successive inflammation via PKCδ-IRAK axis in adipocytes

Chronic inflammation contributes to obesity mediated metabolic disturbances, including insulin resistance. Obesity is associated with altered microbial load in metabolic tissues that can contribute to metabolic inflammation. Different bacterial components such as, LPS, peptidoglycans have been shown to underpin metabolic disturbances through interaction with host innate immune receptors. Activation of Nucleotide-binding oligomerization domain-containing protein 1 (Nod1) with specific peptidoglycan moieties promotes insulin resistance, inflammation and lipolysis in adipocytes. However, it was not clear how Nod1-mediated lipolysis and inflammation is linked. Here, we tested if Nod1-mediated lipolysis caused accumulation of lipid intermediates and promoted cell autonomous inflammation in adipocytes. We showed that Nod1-mediated lipolysis caused accumulation of diacylglycerol (DAG) and activation of PKCδ in 3T3-L1 adipocytes, which was prevented with a Nod1 inhibitor. Nod1-activated PKCδ caused downstream stimulation of IRAK1/4 and was associated with increased expression of proinflammatory cytokines such as, IL-1β, IL-18, IL-6, TNFα and MCP-1. Pharmacological inhibition or siRNA mediated knockdown of IRAK1/4 attenuated Nod1-mediated activation of NF-κB, JNK, and the expression of proinflammatory cytokines. These results reveal that Nod1-mediated lipolysis promoted accumulation of DAG, which engaged PKCδ and IRAK1/4 to augment inflammation in 3T3-L1 adipocytes.     

The aldehyde hypothesis: metabolic intermediates as antimicrobial effectors

There are many reactive intermediates found in metabolic pathways. Could these potentially toxic molecules be exploited for an organism''s benefit? We propose that during certain microbial infections, the production of inherently reactive aldehydes by an infected host is a previously unappreciated innate immune defence mechanism. While there has been a significant focus on the effects of aldehydes on mammalian physiology, the idea that they might be exploited or purposefully induced to kill pathogens is new. Given that aldehydes are made as parts of metabolic programmes that accompany immune cell activation by the cytokine interferon-gamma (IFN-γ) during infections, we hypothesize that aldehydes are among the arsenal of IFN-γ-inducible effectors needed for pathogen control.     

Metabolic regulation of ferroptosis in the tumor microenvironment

Ferroptosis is an iron-dependent, nonapoptotic form of regulated cell death triggered by impaired redox and antioxidant machinery and propagated by the accumulation of toxic lipid peroxides. A compendium of experimental studies suggests that ferroptosis is tumor-suppressive. Sensitivity or resistance to ferroptosis can be regulated by cell-autonomous and non-cell-autonomous metabolic mechanisms. This includes a role for ferroptosis that extends beyond the tumor cells themselves, mediated by components of the tumor microenvironment, including T cells and other immune cells. Herein, we review the intrinsic and extrinsic factors that promote the sensitivity of cancer cells to ferroptosis and conclude by describing approaches to harness the full utility of ferroptotic agents as therapeutic options for cancer therapy.