Immune Recognition Method Based on Analogy Reasoning in Intrusion Detection System

In this paper, we propose an analogy based immune recognition method that focuses on the implement of the clone selection process and the negative selection process by means of analogy similarity. This method is applied in an IDS （Intrusion Detection System） following several steps. Firstly, the initial abnormal behaviours sample set is optimized through the combining of the AIS （Artificial Immune System） and the genetic algorithm. Then, the abnormity probability algorithm is raised considering the two sides of abnormality and normality. Finally, an intrusion detection system model is established based on the above algorithms and models.

Engineered macrophage-biomimetic versatile nanoantidotes for inflammation-targeted therapy against Alzheimer’s disease by neurotoxin neutralization and immune recognition suppression

Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain,leading to neurodegeneration in Alzheimer’s disease(AD).Blocking active recognition of microglia while removing neurotoxins holds promise for fundamentally alleviating neurotoxin-induced immune responses,but is very challenging.Herein,an engineered macrophage-biomimetic versatile nanoantidote(OT-Lipo@M)is developed for inflammation-targeted therapy against AD by neurotoxin neutralization and immune recognition suppression.Coating macrophage membranes can not only endow OT-Lipo@M with anti-phagocytic and inflammation-tropism capabilities to target inflammatory lesions in AD brain,but also efficiently reduce neurotoxin levels to prevent them from activating microglia.The loaded oxytocin(OT)can be slowly released to downregulate the expression of immune recognition site Toll-like receptor 4(TLR4)on microglia,inhibiting TLR4-mediated pro-inflammatory signalling cascade.Benefiting from this two-pronged immunosuppressive strategy,OT-Lipo@M exhibits outstanding therapeutic effects on ameliorating cognitive deficits,inhibiting neuronal apoptosis,and enhancing synaptic plasticity in AD mice,accompanied by the delayed hippocampal atrophy and brain microstructural disruption by in vivo 9.4T MR imaging.This work provides new insights into potential AD therapeutics targeting microglia-mediated neuroinflammation at the source.

Identification and characterization of endosymbiosis-related immune genes in deep-sea mussels Gigantidas platifrons

Deep-sea mussels of the subfamily Bathymodiolinae are common and numerically dominant species widely distributed in cold seeps and hydrothermal vents.During long-time evolution,deep-sea mussels have evolved to be well adapted to the local environment of cold seeps and hydrothermal vents by various ways,especially by establishing endosymbiosis with chemotrophic bacteria.However,biological processes underlying the establishment and maintenance of symbiosis between host mussels and symbionts are largely unclear.In the present study,Gigantidas platifrons genes possibly involved in the symbiosis with methane oxidation symbionts were identified and characterized by Lipopolysaccharide(LPS)pull-down and in situ hybridization.Five immune related proteins including Toll-like receptor 2(TLR2),integrin,vacuolar sorting protein(VSP),matrix metalloproteinase 1(MMP1),and leucine-rich repeat(LRR-1)were identified by LPS pull-down assay.These five proteins were all conserved in either molecular sequences or functional domains and known to be key molecules in host immune recognition,phagocytosis,and lysosome-mediated digestion.Furthermore,in situ hybridization of LRR-1,TLR2 and VSP genes was conducted to investigate their expression patterns in gill tissues of G.platifrons.Consequently,LRR-1,TLR2,and VSP genes were found expressed exclusively in the bacteriocytes of G.platifrons.Therefore,it was suggested that TLR2,integrin,VSP,MMP1,and LRR-1 might be crucial molecules in the symbiosis between G.platifrons and methane oxidation bacteria by participating in symbiosis-related immune processes.

Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic nerve.Still,it is unknown whether olfactory ensheathing glia also have neuroprotective properties.Olfactory ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion cells.Therefore,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve crush.Olfactory ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive treatments.Anatomical and gene expression analyses were performed.Olfactory bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡmolecules.Allogeneically and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an epimembrane.In axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 days.In these retinas,microglial anatomical activation was higher than after optic nerve crush alone.In intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or immunosuppression.However,neuroprotection of axotomized retinal ganglion cells did not improve with these treatments.The different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

Exposure to heat-inactivated Trichophyton rubrum resulting in a limited immune response of human keratinocytes

Background Trichophyton rubrum （T. rubrum） represents the most important agent of dermatophytosis in humans. T. rubrum infection causes slight inflammation, and tends to be chronic and recurrent. It is suggested that it may result from the failure of epithelial cells to recognize T. rubrum effectively and initiate effective immune responses. The C-type lectin receptors （CLR） and toll-like receptors （TLR） are the two major pattern recognition receptors （PRRs） that recognize fungal components. Therefore, the purpose of the study was to analyze the expression of those PRRs and the cytokines in HaCaT cells stimulated with heat-inactivated T. rubrum conidia and hyphae, respectively. Methods HaCaT cells were unstimulated or stimulated with heat-inactivated T. rubrum conidia and hyphae （l×106 and 1.5×105 colony-forming unit （CFU） in 2 ml medium, respectively） for 6, 12 and 24 hours. The mRNA expression of PRRs involved in recognizing fungal pathogen-associated molecular patterns （PAMPs） and signaling molecules were measured by quantitative reverse transcription polymerase chain reaction （RT-PCR）. Meanwhile, surface toll-like receptor （TLR） 2, TLR4 and Dectin-1 were analyzed by fluorescence-activated cell sorter （FACS） 24 hours after treatment. The cytokines were detected in cell culture supernatants of HaCaT cells in 12 and 24 hours after treatment. Results HaCaT cells constitutively expressed mRNA of membrane-bound TLR1,2, 4 and 6, Dectinl and DC-SIGN, but not Dectin-2 or Mincle. Heat-killed T. rubrum did not significantly upregulate gene transcriptions of the PRRs of HaCaT cells. Heat-inactivated T. rubrum conidia significantly reduced the surface expression of TLR2 and Dectin-1, and suppressed the secretions of interferon-inducible protein-10 （IP-10） and monocyte chemotactic protein-1 （MCP-1） of HaCaT cells, while heat-killed T. rubrum hyphae significantly induced the secretions of IP-10 and MCP-I. Conclusion The cell-wall antigens of T. rubrum fail to activate transcriptional expression of PRRs and induce a lower immune response of HaCaT cells by limited cytokines secretion.

Microbe-derived non-necrotic glycoside hydrolase family 12 proteins act as immunogenic signatures triggering plant defenses

Plant pattern recognition receptors(PRRs)are sentinels at the cell surface sensing microbial invasion and activating innate immune responses.During infection,certain microbial apoplastic effectors can be recognized by plant PRRs,culminating in immune responses accompanied by cell death.However,the intricated relationships between the activation of immune responses and cell death are unclear.Here,we studied the glycoside hydrolase family12(GH12)protein,Ps109281,secreted by Phytophthora sojae into the plant apoplast during infection.Ps109281 exhibits xyloglucanase activity,and promotes P.sojae infection in a manner dependent on the enzyme activity.Ps109281 is recognized by the membranelocalized receptor-like protein RXEG1 and triggers immune responses in various plant species.Unlike other characterized GH12 members,Ps109281 fails to trigger cell death in plants.The loss of cell death induction activity is closely linked to a sequence polymorphism at the Nterminus.This sequence polymorphism does not affect the in planta interaction of Ps109281 with the recognition receptor RXEG1,indicating that cell death and immune response activation are determined using different regions of the GH12 proteins.Such GH12 protein also exists in other Phytophthora and fungal pathogens.Taken together,these results unravel the evolution of effector sequences underpinning different immune outputs.

Expression of Innate Immunity Genes in Epithelial Cells of Hypertrophic Adenoids with and without Pediatric Chronic Rhinosinusitis： A Preliminary Report

Background： Adenoid hypertrophy （AH） is associated with pediatric chronic rhinosinusitis （pCRS）, but its role in the inflammatory process of pCRS is unclear. It is thought that innate immunity gene expression is disrupted in the epithelium of patients with chronic rhinosinusitis （CRS）, including antimicrobial peptides and pattern recognition receptors （PRRs）. The aim of this preliminary study was to detect the expression of innate immunity genes in epithelial cells of hypertrophic adenoids with and without pCRS to better understand their role in pCRS. Methods： Nine pCRS patients and nine simple AH patients undergoing adenoidectomy were recruited for the study. Adenoidal epithelium was isolated, and real-time quantitative polymerase chain reaction （RT-qPCR） was employed to measure relative expression levels of the following messenger RNAs in hypertrophic adenoid epithelial cells of pediatric patients with and without CRS： Human β-defensin （HBD） 2 and 3, surfactant protein （SP）-A and D, toll-like receptors 1-10, nucleotide-binding oligomerization domain （NOD）-like receptors NOD 1, NOD 2, and NACHT, LRR and PYD domains-containing protein 3, retinoic acid-induced gene 1, melanoma differentiation-associated gene 5, and nuclear factor-riB （NF-KB）. RT-qPCR data from two groups were analyzed by independent sample t-tests and Mann-Whitney U-tests. Results： The relative expression of SP-D in adenoidal epithelium ofpCRS group was significantly lower than that in AH group （pCRS 0.73 ± 0.10 vs. AH 1.21 ±0.15; P = 0.0173, t = 2.654）. The relative expression levels of all tested PRRs and NF-κB, as well as HBD-2, HBD-3, and SP-A, showed no statistically significant differences in isolated adenoidal epithelium between pCRS group and AH group. Conclusions： Down-regulated SP-D levels in adenoidal epithelium may contribute to the development of pCRS. PRRs, however, are unlikely to play a significant role in the inflammatory process ofpCRS.