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关键词： MHC   Amphibia   Immune system   Immunity   HLA  

摘要： The major histocompatibility complex (MHC) is a cluster of functionally related genes encoding proteins which, among other functions, mediate immune system activation. While the MHC of many vertebrates has been extensively studied, less is known about the amphibian MHC. This represents an important knowledge gap because amphibians mark the evolutionary transition from an aquatic to a terrestrial lifestyle and often maintain a biphasic lifestyle. Hence, they tend to be exposed to both aquatic and terrestrial pathogen communities, providing opportunities to gain fundamental insights into how the immune system responds to different environmental challenges. Moreover, amphibians are globally threatened by invasive pathogens and the MHC may play a role in combating population decline. In this review, we summarize the current state of knowledge regarding the amphibian MHC and identify the major differences with other vertebrates. We also review how the number of MHC gene copies varies across amphibian groups and how MHC-based variation relates to amphibian ontogeny, behaviour, disease, and phylogeography. We conclude by identifying knowledge gaps and proposing priorities for future research.

关键词： alpha-Hemolysin protein   Aptamer   Real-time PCR   Apta-qPCR  

摘要： Alpha-toxin of Staphylococcus aureus belongs to the pore-forming toxin (PFT) family, which can lyse red and white blood cells. In addition to the existence of the hla gene in the majority of S. aureus strains (about 95 %), higher expression exhibits enhanced pathogenicity to the bacteria. Various methods, such as antibodies and aptamers, could serve to detect this toxin. In the current study, for the first time, an improved sandwich aptamerantibody-based method was developed using specific murine polyclonal antibodies and a specific aptamer to detect a wide range of alpha-toxin levels. Denatured recombinant alpha-toxin was administered to mice to trigger the production of specific antibodies, which were subsequently purified from immune sera. These antibodies served as capturers in the designed apta-qPCR assay, with an aptamer employed as a detector. The results showed that spiked alpha-toxin in the undiluted serum samples could detect alpha-toxin between 300 and 0.5 ng/mL with no cross- reactivity. The coefficient of variation (CV) percent of intra- and inter-assays were 0.84 and 1.06, respectively. Since in the apta-qPCR assay, a combination of specific polyclonal antibodies as capture and specific aptamer along with real-time PCR (qPCR) sensitivity is used, this robust method could be used in diagnostic laboratories to detect various levels of the toxin in human serum samples.

关键词： IL-33   Allergic asthma   Age   Type 2 responses  

摘要： Epithelial-derived cytokines, especially type 2 alarmins (TSLP, IL-25, and IL-33), have emerged as critical mediators of type 2 inflammation. IL-33 attracts more interest for its strong association with allergic asthma, especially in childhood asthma. However, the age-dependent role of IL-33 to the development of allergic asthma remains elusive. Here, using OVA-induced allergic asthma model in neonatal and adult mice, we report that IL-33 is the most important alarmin in neonatal lung both at steady state or inflammation. The deficiency of IL-33/ST2 abrogated the development of allergic asthma only in neonates, whereas in adults the effect was limited. Interestingly, the deficiency of IL-33/ST2 equally dampened the ILC2 responses in both neonatal and adult models. However, the effect of IL-33/ST2 deficiency on Th2 responses is age-dependent, which is only blocked in neonates. Furthermore, IL-33/ST2 signaling is dispensable for OVA sensitization. Following OVA challenge in adults, the deficiency of IL-33/ST2 results in compensational more TSLP, which in turn recruits and activates lung DCs and boosts Th2 responses. The enriched gamma delta T17 cells in IL-33/ST2 deficient neonatal lung suppress the expression of type 2 alarmins, CCL20 and GM-CSF via IL-17A, thus might confer the inhibition of allergic asthma. Finally, on the basis of IL-33 deficiency, the additive protective effects of TSLP blocking is much more pronounced than IL-25 blocking in adults. Our studies demonstrate that the role of IL-33 for ILC2 and Th2 responses varies among ages in OVA models and indicate that the factor of age should be considered for intervention of asthma.

关键词： HLA-DQB1*03:571   new allele   next-generation sequencing  

摘要： HLA-DQB1*03:571 differs from HLA-DQB1*03:09 by one nucleotide substitution in codon 170 in exon 3.

摘要： [This corrects the article DOI: 10.1039/c5tx00164a.].

关键词： HLA-A   next generation sequencing   null allele  

摘要： HLA-A*02:1195N differs from HLA-A*02:01:01:01 by one nucleotide substitution in exon 4, at gDNA position 1843 (G>A).

关键词： HLA-C*14:02:41   next-generation sequencing   synonymous substitution  

摘要： The HLA-C*14:02:41 allele is distinguished from HLA-C*14:02:01:01 by a single synonymous change at c.606G>C.

关键词： fisetin   IFN-gamma   macrophages   inflammation   RNA-Seq   cellular metabolism   IRF1  

摘要： Although interferon-gamma (IFN-gamma) is known as a critical factor in polarizing macrophages into the pro-inflammatory state for immune response, how dietary flavonoids regulate IFN-gamma response for anti-inflammation is incompletely elucidated. This study aims to investigate the effect of fisetin, a typical flavonol, on the inhibition of IFN-gamma-induced inflammation by RNA sequencing (RNA-Seq) and cellular metabolism analysis. RAW264 macrophages pretreated with fisetin following IFN-gamma stimulation were subjected to RNA-Seq to analyze alterations in gene expression. Cellular signaling and transcription were investigated using enrichment analysis, motif analysis, and transcription factor prediction. Cellular metabolic state was assessed by measuring the oxygen consumption rate (OCR) and lactate level to reflect mitochondrial respiration and glycolysis. Alterations in signaling proteins were confirmed by Western blot. The results revealed that fisetin downregulated the IFN-gamma-induced expression of pro-inflammatory genes and M1 marker genes such as Cxcl9, Il6, Cd80, Cd86, and Nos2. In cellular metabolism, fisetin upregulated the oxidative phosphorylation (OXPHOS) pathway, restored impaired OCR, and reduced lactate production induced by IFN-gamma. Motif analysis suggested that fisetin suppressed the activation of IFN-regulatory factor 1 (IRF1). Western blot data further confirmed that fisetin inhibited the phosphorylation of Jak1, Jak2, and STAT1, and decreased the nuclear accumulation of phosphorylated STAT1 and IRF1 induced by IFN-gamma. Taken together, our data revealed that fisetin is a potent flavonoid that attenuates IFN-gamma-stimulated murine macrophage inflammation and ameliorates disrupted cellular metabolism with a possible Jak1/2-STAT1-IRF1 pathway.