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Molecular Immunology
Pergamon Press
Molecular Immunology

Pergamon Press

0161-5890

Molecular Immunology/Journal Molecular ImmunologySCIISTP
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    Synergistic activity between beta-lactams and igy antibodies against Pseudomonas aeruginosa in vitro

    Sanches, Renata FernandesFerraro, Ana Carolina Navarro dos SantosMarroni, Floristher Elaine CarraraVenancio, Emerson Jose...
    5页
    查看更多>>摘要：Multi-drug resistant Pseudomonas aeruginosa is a gram-negative bacillus responsible for nosocomial infections. Immunoglobulin Y (IgY) is a chicken immunoglobulin used for research, immunodiagnosis, and immunotherapy. IgY presents antimicrobial properties and it is under investigation for use as an adjunct to prophylactic therapies. The current study aimed to assess the synergistic action between anti-P aeruginosa IgY and the beta-lactams ceftazidime, imipenem, and meropenem. IgY antibodies were obtained from laying hens immunized with SPM-1 producing P. aeruginosa (Pa48spm-1+) or VIM-2 producing P. aeruginosa (Pa23vim-2 +). The antimicrobial activity of IgY antibodies was evaluated by the growth inhibition test, and the synergistic effect was assessed by determination of the fractional inhibitory concentration index. Anti-Pa48spm-1+ IgY shows antimicrobial activity at 1.25 mg/ml and anti-Pa23vim-2+ IgY shows antimicrobial activity at 2.5 mg/ml. The fractional inhibitory concentration indices of anti-Pa48spm-1+ IgY and ceftazidime, or imipenem, or meropenem at 72 h of experiment were 0.189, 0.209, and 0.440, respectively. For anti-Pa23vim-2+ IgY, the fractional inhibitory concentration indices were 0.440 with ceftazidime, 0.453 with imipenem, and 0.441 with meropenem at 72 h. We conclude that there is a synergistic action between anti-P. aeruginosa IgY and the antimicrobials tested. Further studies are necessary to investigate the mechanisms associated with this action.
      原文链接:
    • NSTL
    • Elsevier

    Regulation and function of Id2 in plasmacytoid dendritic cells

    Babcock, Rachel L.Zhou, YifanPatel, BhaktiChrisikos, Taylor T....
    12页
    查看更多>>摘要：Plasmacytoid dendritic cells (pDCs) are specialized type I interferon (IFN-I) producing cells that promote anti-viral immune responses and contribute to autoimmunity. Development of pDCs requires the transcriptional regulator E2-2 and is opposed by inhibitor of DNA binding 2 (Id2). Prior work indicates Id2 is induced in pDCs upon maturation and may affect pDC IFN-I production via suppression of E2-2, suggesting an important yet uncharacterized role in this lineage. We found TLR7 agonists stimulate Id2 mRNA and protein expression in pDCs. We further show that transcriptional activation of Id2 is dependent on the E2 ubiquitin-conjugating enzyme Ubc13, but independent of IFN-I signaling in response to TLR7 agonist stimulation. Nonetheless, con-ditional Id2 depletion in pDCs indicates Id2 is dispensable for TLR7 agonist-induced maturation and inhibition of E2-2 expression. Thus, we identify new mechanisms of Id2 regulation by Ubc13, which may be relevant for understanding Id2 gene regulation in other contexts, while ruling out major roles for Id2 in pDC responses to TLR7 agonists.
      原文链接:
    • NSTL
    • Elsevier

    Immunoglobulin gene expression profiles and microbiome characteristics in periodontitis in nonhuman primates

    Gonzalez, Octavio A.Ebersole, Jeffrey L.Nagarajan, RadhakrishnanKirakodu, Sreenatha S....
    16页
    查看更多>>摘要：Colonization of mucosal tissues throughout the body occurs by a wide array of bacteria in the microbiome that stimulate the cells and tissues, as well as respond to changes in the local milieu. A feature of periodontitis is the detection of adaptive immune responses to members of the oral microbiome that show specificity and changes with disease and treatment. Thus, variations in antibody responses are noted across the population and affected by aging, albeit, data are still unclear as to how these differences relate to disease risk and expression. This study used a nonhuman primate model of experimental periodontitis to track local microbiome changes as they related to the use and expression of a repertoire of immunoglobulin genes in gingival tissues. Gingival tissue biopsies from healthy tissues and following ligature-placement for disease initiation and progression provided gene expression analysis. Additionally, following removal of the ligatures, clinical healing occurs with gene expression in disease resolved tissues. Groups of 9 animals (young: < 3 yrs., adolescent: 3-7 yrs., adult -12 to 15 yrs.; aged: 17-22 yrs) were used in the investigation. In healthy tissues, young and adolescent animals showed levels of expression of 78 Ig genes that were uniformly less than adults. In contrast, 2/3 of the Ig genes were elevated by > 2-fold in the aged samples. Specific increases in an array of the Ig gene transcripts were detected in adults at disease initiation and throughout progression, while increases in young and adolescent animals were observed only with disease progression, and in aged samples primarily late in disease progression. Resolved lesions continued to demonstrate elevated levels of Ig gene expression in only young, adolescent and adult animals. The array of Ig genes significantly correlated with inflammatory, tissue biology and hypoxia genes in the gingival tissues, with variations associated with age. In the young group of animals, specific members of the oral microbiome positively correlated with Ig gene expression, while in the older animals, many of these correlations were negative. Significant correlations were observed with a select assortment of bacterial OTUs and multiple Ig genes in both younger and older animal samples, albeit the genera/species showed little overlap. Incorporating this array of microbes and host responses clearly discriminated the various time points in transition from health to disease and resolution in both the young and adult animals. The results support a major importance of adaptive immune responses in the kinetics of periodontal lesion formation, and support aging effects on the repertoire of Ig genes that may relate to the increased prevalence and severity of periodontitis with age.
      原文链接:
    • NSTL
    • Elsevier

    QKI deficiency in macrophages protects mice against JEV infection by regulating cell migration and antiviral response

    Deng, LeleWang, WenwenBian, PeiyuWu, Mengqi...
    11页
    查看更多>>摘要：Japanese encephalitis (JE) is a major reason to cause viral encephalitis, with 50% patients suffering from severe neuro-inflammation and permanent neural injury. Effective anti-viral treatment is urgently needed. Here, we found RNA binding protein quaking (QKI) was involved in the progression of JE by regulating migration and anti-viral response of macrophages. After JE virus (JEV) infection, QKI-deficient mice had lower viral loads in the brain and fewer neurological symptoms. In comparison with control mice, proinflammatory cytokines in the brain of QKI-deficient animals revealed distinct patterns, with lower levels of IL-6 (interleukin-6) and IFN-beta (interferon-beta) at the early stage but higher levels at the end of JE. Then we found infiltration of CCR2 positive ((C-C motif) receptor 2) peripheral macrophages and CCR2 expression on macrophages were inhibited in QKIdeficient mice, while the expression of CCR2 ligands was not changed. Bioinformatical analysis showed that a QRE (quaking response element) located on 3 ' UTR (untranslated region) of Ccr2. We further verified that QKI was able to interact with Ccr2 mRNA and regulate its degradation in vitro. Additionally, since the IFN-beta production was increased in QKI-ablation mice after JEV infection, the anti-viral response was analyzed. Results in QKI-silenced N9 cells showed that the expression of RIG-I (retinoic acid-inducible gene-I) and TBK1 (TANK binding kinase 1) was increased, thus further inducing IRF3 (interferon regulatory factor 3) phosphorylation and interferon activation. Overall, these results revealed QKI mediated the anti-viral process via interfering migration of macrophages to CNS (central nervous system) and enhancing RIG-I/IRF3/IFN-beta pathway to restrict virus dissemination.
      原文链接:
    • NSTL
    • Elsevier

    Clostridium haemolyticum, a review of beta toxin and insights into the antigen design for vaccine development

    Alves, Mariliana Luiza FerreiraFerreira, Marcos Roberto AlvesRodrigues, Rafael RodriguesConceicao, Fabricio Rochedo...
    9页
    查看更多>>摘要：Phospholipases C (PLCs) represent an important group of lethal toxins produced by pathogenic bacteria of the Clostridium genus, including the beta toxin of C. haemolyticum. Bacillary hemoglobinuria in cattle and sheep is the main disease caused by this pathogen and its incidence can be reduced by annual vaccination of herds. Currently, widely used vaccines depend on cultivating the pathogen and obtaining high concentrations of the toxin, disadvantages that can be overcome with the use of recombinant vaccines. In the development of this new generation of immunizing agents, identifying and understanding the structural and immunological aspects of the antigen are crucial steps, but despite this, the beta toxin is poorly characterized. Fortunately, the time and resources required for these investigations can be reduced using immunoinformatics. To advance the development of recombinant vaccines, in addition to a brief review of the structural and immunological aspects of beta toxin, this work provides in silico mapping of immunodominant regions to guide future vaccinology studies against C. haemolyticum. A review of alternatives to overcome the limitations of beta toxin vaccines (conventional or recombinant) is also proposed.
      原文链接:
    • NSTL
    • Elsevier

    Nrf2 Activation and NF-Kb & caspase/bax signaling inhibition by sodium butyrate alleviates LPS-induced cell injury in bovine mammary epithelial cells

    Ali, IlyasLi, ChengminKuang, MeqianShah, Abid Ullah...
    14页
    查看更多>>摘要：Mastitis, an inflammation of the mammary gland, is a complex disease that affects the health of dairy cows worldwide. Sodium butyrate (SB) is a short-chain fatty acid that has recently been shown to have antioxidant, anti-inflammatory and anti-apoptotic potential in various cells types, although its role in bovine mammary epithelial cells (bMECs) has not been comprehensively reported. Therefore, the aim of this study was to assess the protective effect of sodium butyrate on Lipopolysaccharide (LPS)-induced mastitis model in vitro and to elucidate the possible underlying molecular mechanisms. The in vitro mastitis model was designed to investigate the regulatory effect of SB on LPS-induced inflammatory conditions in bMECs, with particular emphasis on oxidative stress, inflammatory response, apoptosis, and mitochondrial dysfunction. The results showed that SB cotreatment markedly prevented LPS-induced death of bMECs in a concentration-dependent manner. In addition, SB attenuated LPS-induced oxidative stress (OS) (Increased Intracellular ROS, MDA, and decreased SOD, GSH-Px and CAT activity), thereby reduced inflammation (increased expression of IL-6, IL-I beta, and TNF-alpha), and apoptosis (Increased the expression of caspases and Bax and decreased Bcl-2) via inhibiting NF-kB and caspase/ bax signaling pathways. Furthermore, the protective effect of SB was also associated with the activation of endogenous antioxidant system (Nrf2, Keap1, NQO-1 and HO-1). Nrf2 silencing significantly abolished the protective effect of SB on bMECs. In conclusion, our findings suggest that SB has a significant protective effect on LPS-induced OS, inflammatory responses and apoptosis by activating Nrf2 and inhibiting NF-kB and ROSmediated mitochondrial dysfunction. These results propose that SB may be an important regulator of OS and its subsequent inflammatory responses, and thus could be used as a therapeutic agent for bovine mastitis.
      原文链接:
    • NSTL
    • Elsevier

    HIV-1 Gag and Vpr impair the inflammasome activation and contribute to the establishment of chronic infection in human primary macrophages

    Galvao-Lima, Leonardo J.Zambuzi, Fabiana A.Soares, Luana S.Fontanari, Caroline...
    13页
    查看更多>>摘要：The successful establishment of HIV-1 infection is related to inflammasome blocking or inactivation, which can result in the viral evasion of the immune responses and formation of reservoirs in several tissues. In this sense, we aimed to evaluate the viral and cellular mechanisms activated during HIV-1 infection in human primary macrophages that allow an effective viral replication in these cells. We found that resting HIV-1-infected macrophages, but not those activated in classical or alternative patterns, released IL-1 beta and other pro-inflammatory cytokines, and showed increased CXCL10 expression, without changes in the NLRP3, AIM2 or RIG-I inflammasome pathways. Also, similar levels of Casp-1, phosphorylated NF-kappa B (p65) and NLRP3 proteins were found in uninfected and HIV-1-infected macrophages. Likewise, no alterations were detected in ASC specks released in the culture supernatant after HIV-1 infection, suggesting that macrophages remain viable after infection. Using in silico prediction studies, we found that the HIV-1 proteins Gag and Vpr interact with several host proteins. Comparable levels of trans-LTB4 were found in the supernatants of uninfected and HIV-1-infected macrophages, whereas ROS production was impaired in infected cells, which was not reversed after the PMA stimulus. Immunofluorescence analysis showed structural alterations in the mitochondrial architecture and an increase of BIM in the cytoplasm of infected cells. Our data suggest that HIV-1 proteins Gag and Vpr, through interacting with cellular proteins in the early steps of infection, preclude the inflammasome activation and the development of effective immune responses, thus allowing the establishment of the infection.
      原文链接:
    • NSTL
    • Elsevier

    Transcriptomics analysis provides new insights into the fish antiviral mechanism and identification of interferon-stimulated genes in grass carp (Ctenopharyngodon idella)

    Wang, XiaodongChen, DunxueLv, ZhaoZhao, Xin...
    10页
    查看更多>>摘要：Grass carp is an economically important freshwater fish in China, and haemorrhagic disease caused by GCRV has seriously restricted its farming scale. To understand the host molecular basis for antiviral defence and explore the effector molecules, a global transcriptional profiling of four major immune tissues (liver, spleen, head kidney, and trunk kidney) of GCRV-infected grass carp was established. A total of 192.65 Gb clean data was obtained with 6.11 Gb per sample and stored in the NCBI Sequence Read Archive (with accession number PRJNA759556). Based on the GO and KEEG analyses, 108 unique GO terms were enriched in the four tissues. Thirty-five enriched pathways were obtained, with 21 metabolism-related pathways mainly gained in the liver and trunk kidney, and 14 immune response pathways were enriched in the spleen and head kidney. Also demonstrated was that GCRV stimulates not only the expression of interferon-stimulated genes (ISGs) but also proinflammatory cytokines. 27 ISGs were screened from the candidate DEGs, and eight ISGs were identified for the first time in grass crap. These ISGs were classified into three categories by their function found in mammals: (i) positively regulates the IFN signalling pathway (RIG-I, MDA5, IRF7, IRF9, STAT2, and TRIM25); (ii) negatively regulates the IFN signalling pathway (usp18 and SOCS1); and (iii) exerts direct antiviral activity such as Mx1, ISG15, ISG56, ISG58, viperin, and PKR. Eight major ISGs and four typical differentially inflammatory cytokines were used for further expression analysis with prominent expression in the liver, spleen and kidney. The onset time of IFN-mediated antiviral response was trunk kidney (12-24 h) > liver (48 h) > spleen (96-120 h), and the intensity was liver > spleen > trunk kidney. Notably, the inflammatory reaction occurs early in the liver and trunk kidney. This result implies that ISGs may act synergistically and that the IFN response is closely related to the inflammatory response against GCRV infection. The transcriptomic profiles obtained and the function of ISGs predicted in this study provide new insights into fish antiviral mechanisms and developing effective therapeutic directions.
      原文链接:
    • NSTL
    • Elsevier