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Innate Immunity

Nam V Nguyen, James T Tran, David Jesse Sanchez
This study investigates the modulation of Type I IFN induction of an antiviral state by HIV. IFNs, including IFN-α, are key innate immune cytokines that activate the JAK/STAT pathway leading to the expression of IFN-stimulated genes. IFN-stimulated gene expression establishes the antiviral state, limiting viral infection in IFN-α-stimulated microenvironments. Our previous studies have shown that HIV proteins disrupt the induction of IFN-α by degradation of IFN-β promoter stimulator-1, an adaptor protein for the up-regulation and release of IFN-α into the local microenvironment via the retinoic acid-inducible gene 1-like receptor signaling pathway...
October 3, 2018: Innate Immunity
Guangsheng Wan, Manli Xie, Hongjie Yu, Hongyu Chen
In this study we investigated the association between intestinal dysbacteriosis with colorectal cancer progress and the underlying molecular mechanisms. Tumor progression was evaluated using xenograft mice model. The epithelial-mesenchymal transition (EMT) markers were quantified by both real-time PCR and immunoblotting. The serum content of IL-6 and TNF-α were measured with ELISA kits. Cell proliferation was determined by the Cell Counting Kit-8. Intestinal dysbacteriosis was successfully simulated by the administration of a large dose of antibiotics and was demonstrated to promote xenograft tumor growth and induce EMT...
September 23, 2018: Innate Immunity
José E Belizário, Jennifer M Neyra, Maria Fernanda Setúbal Destro Rodrigues
NK cells are innate lymphoid cells that exert a key role in immune surveillance through the recognition and elimination of transformed cells and viral, bacterial, and protozoan pathogen-infected cells without prior sensitization. Elucidating when and how NK cell-induced intracellular microbial cell death functions in the resolution of infection and host inflammation has been an important topic of investigation. NK cell activation requires the engagement of specific activating, co-stimulatory, and inhibitory receptors which control positively and negatively their differentiation, memory, and exhaustion...
September 20, 2018: Innate Immunity
Jiangtao Pu, Xiaojun Tang, Xiang Zhuang, Zhi Hu, Kaiming He, Yunfei Wu, Tianyang Dai
This study mainly investigated the effects of matrine on cell apoptosis and the effects of anticancer drugs in non-small cell lung cancer (NSCLC) cell lines (A549 and LK2 cells). The results showed that matrine (≥10 μM) caused a significant inhibition on cell viability and 10 and 100 μM matrine induced cell apoptosis via influencing p53, bax, casp3, and bcl-2 expressions in A549 cells. In addition, matrine significantly down-regulated C-C chemokine receptor type 7 (CCR7) expression, and blocking the down-regulation of CCR7 by exogenous chemokine ligand 21 (CCL21) treatment alleviated matrine-caused effects of apoptosis genes in A549 cells...
September 20, 2018: Innate Immunity
Julien Rs Dandrieux, Lina Maria Martinez Lopez, Andrew Stent, Albert Jergens, Karin Allenspach, Cameron J Nowell, Simon M Firestone, Wayne Kimpton, Caroline S Mansfield
Chronic enteropathy (CE) in dogs is characterized retrospectively per treatment response as food-responsive enteropathy (FRE), antibiotic-responsive enteropathy (ARE), and immunosuppressant-responsive enteropathy (IRE) - the latter most resembling inflammatory bowel disease in people. The aim of this study was to characterize duodenal macrophages (Mϕ) in CE using immunohistochemistry; with calprotectin (CAL) as a marker of early differentiated Mϕ and CD163 expression as a marker for resident Mϕ in the duodenum before and after treatment...
September 17, 2018: Innate Immunity
Charys Palmer, Francesco Peri, Frank Neumann, Feroz Ahmad, David S Leake, Grisha Pirianov
TLRs, including TLR4, have been shown to play a crucial role in cardiovascular inflammatory-based diseases. The main goal of this study was to determine the potential of FP7, a synthetic glycolipid active as a TLR4 antagonist, to modulate haematopoietic and non-haematopoietic vascular TLR4 pro-inflammatory signalling. HUVEC, human THP-1 monocytes, THP-1-derived macrophages, mouse RAW-264.7 macrophages and Angiotensin II-infused apolipoprotein E-deficient mice were in vitro and in vivo models, respectively. Western blotting, Ab array and ELISA approaches were used to explore the effect of FP7 on TLR4 functional activity in response to bacterial LPS ( in vitro) and endogenous ligands of sterile inflammation ( in vitro and in vivo)...
September 12, 2018: Innate Immunity
Kata Tombácz, Gregg Burgess, Angela Holder, Arno Werners, Dirk Werling
Toxoplasma gondii is responsible for one of the most prevalent infections in people. T. gondii profilin (TgPr) is a protein integral to parasite movement and cellular invasion. Murine TLRs has been described to bind TgPr. Furthermore, more recently, human TLR5 has been described to recognise recombinant TgPr, as well as bacterial flagellin. In addition to infections in humans, T. gondii infects farm animals, but little information is available about its innate recognition. We aimed to investigate whether, similarly to their human orthologue, bovine and porcine TLR5 could also be stimulated by TgPr by using a combination of reporter cell lines expressing full length TLR5 from each species as well as primary cells...
September 8, 2018: Innate Immunity
Erdenezaya Odkhuu, Takayuki Komatsu, Naoki Koide, Yoshikazu Naiki, Kenji Takeuchi, Yukie Tanaka, Bilegtsaikhan Tsolmongyn, Ulziisaikhan Jambalganiin, Naoko Morita, Tomoaki Yoshida, Bin Gotoh, Takashi Yokochi
To suppress virus multiplication, infected macrophages produce NO. However, it remains unclear how infecting viruses then overcome NO challenge. In the present study, we report the effects of accessory protein C from Sendai virus (SeV), a prototypical paramyxovirus, on NO output. We found that in RAW264.7 murine macrophages, a mutant SeV without C protein (4C(-)) significantly enhanced inducible NO synthase (iNOS) expression and subsequent NO production compared to wild type SeV (wtSeV). SeV 4C(-) infection caused marked production of IFN-β, which is involved in induction of iNOS expression via the JAK-STAT pathway...
September 6, 2018: Innate Immunity
Joonas Liukkonen, Ulvi K Gürsoy, Eija Könönen, Mervi Gürsoy, Jari Metso, Aino Salminen, Elisa Kopra, Matti Jauhiainen, Päivi Mäntylä, Kåre Buhlin, Susanna Paju, Timo Sorsa, Markku S Nieminen, Marja-Liisa Lokki, Juha Sinisalo, Pirkko J Pussinen
Genetic factors play a role in periodontitis. Here we examined whether the risk haplotype of MHC class III region BAT1-NFKBIL1-LTA and lymphotoxin-α polymorphisms associate with salivary biomarkers of periodontal disease. A total of 455 individuals with detailed clinical and radiographic periodontal health data were included in the study. A 610 K genotyping chip and a Sequenom platform were used in genotyping analyses. Phospholipid transfer protein activity, concentrations of lymphotoxin-α, IL-8 and myeloperoxidase, and a cumulative risk score (combining Porphyromonas gingivalis, IL-1β and matrix metalloproteinase-8) were examined in saliva samples...
September 3, 2018: Innate Immunity
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No abstract text is available yet for this article.
August 2018: Innate Immunity
Huapei Zhu, Hanwei Jiao, Xin Nie, Baobao Li, Kailian Xu, Feng Pang, Ruiyong Cao, Shu Zhu, Xiaojian Yang, Zhenxing Zhang, Dongmei Peng, Yaying Li, Guohua Li, Haifeng Huang, Chuangfu Chen, Li Du, Fengyang Wang
Brucellosis is a worldwide zoonosis caused by Brucella species and represents a serious threat to both human and animal health. Omp25 is an important immunogenic and protective antigen in Brucella species; however, the functional mechanism of Omp25 in macrophages has not yet been elucidated. Here, we constructed a Brucella melitensis omp25 deletion mutant (M5-90-Δ omp25) and performed microRNA (miRNA) profiling of infected RAW264.7 cells. Eight differentially expressed miRNAs ( mmu-miR-146a-5p, mmu-miR-155-5p, mmu-miR-3473a, mmu-miR-149-3p, mmu-miR-671-5p, mmu-miR-1224-5p, mmu-miR-1895, and mmu-miR-5126) were identified, with quantitative real-time PCR (qRT-PCR) analysis confirming the up-regulation of mmu-miR-146-a-5p and mmu-miR-155-5p and down-regulation of mmu-miR-149-3p and mmu-miR-5126...
August 2018: Innate Immunity
Sabari Nath Neerukonda, Sanjana Mahadev-Bhat, Bridget Aylward, Casey Johnson, Chandrashekhar Charavaryamath, Ryan J Arsenault
Exacerbated inflammation upon persistent barn organic dust exposure is a key contributor to the pathogenesis of lung inflammation and lung function decline. Barn dust constituents and the mechanisms contributing to the exacerbated inflammation are not clearly known. We set out to understand the inflammatory effects of Swine Barn Dust Extracts (SBDE) on human lung epithelial (BEAS2B) and macrophage (THP-1 monocyte derived) cell lines on a kinome array to determine phosphorylation events in the inflammatory signaling pathways...
August 2018: Innate Immunity
Matthew E Long, Ke-Qin Gong, Joseph S Volk, William E Eddy, Mary Y Chang, Charles W Frevert, William A Altemeier, Michael Gale, W Conrad Liles, Anne M Manicone
Matrix metalloproteinases (MMPs) are transcriptionally regulated proteases that have multiple roles in modifying the extracellular matrix (ECM) and inflammatory response. Our previous work identified Mmp28 as a key regulator of inflammation and macrophage polarization during experimental models of pulmonary infection, fibrosis, and chronic smoke exposure. However, the signaling pathways responsible for regulation of macrophage Mmp28 expression remain undefined. This study utilized murine macrophages obtained from wild type, Tlr2-/- , Tlr4-/- , MyD88-/- , Ticam1 Lps2 ( Trifmutant ), and Ifnar1-/- mice to test the hypothesis that macrophage Mmp28 expression was dependent on TRIF and type I IFN...
August 2018: Innate Immunity
Carsten Deppermann, Paul Kubes
Platelets are the main players in thrombosis and hemostasis; however they also play important roles during inflammation and infection. Through their surface receptors, platelets can directly interact with pathogens and immune cells. Platelets form complexes with neutrophils to modulate their capacities to produce reactive oxygen species or form neutrophil extracellular traps. Furthermore, they release microbicidal factors and cytokines that kill pathogens and influence the immune response, respectively. Platelets also maintain the vascular integrity during inflammation by a mechanism that is different from classical platelet activation...
August 2018: Innate Immunity
Jelena Patrnogic, Christa Heryanto, Ioannis Eleftherianos
The common fruit fly Drosophila melanogaster is an exceptional model for dissecting innate immunity. However, our knowledge on responses to parasitic nematode infections still lags behind. Recent studies have demonstrated that the well-conserved TGF-β signaling pathway participates in immune processes of the fly, including the anti-nematode response. To elucidate the molecular basis of TGF-β anti-nematode activity, we performed a transcript level analysis of different TGF-β signaling components following infection of D...
August 2018: Innate Immunity
Colin Martin, Mikita Patel, Sparkle Williams, Hamish Arora, Brian Sims
Human breast milk has been shown to reduce the incidence of necrotizing enterocolitis (NEC). Breast milk has many components (immunoglobulins, proteins, fat, and, of recent interest, exosomes), but the specific component that affords protection against NEC is not known. Exosomes are small-nanometer vesicles that are rich in protein, lipid, and microRNA. Here, we hypothesized that human breast milk-derived exosomes can protect intestinal epithelial cells (IECs) from cell death. Human breast milk was collected, separated using ultracentrifugation, and quantified using NanoSight tracking analysis...
July 2018: Innate Immunity
Jiwei Wang, Peng Wang, Hao Tian, Feng Tian, Ying Zhang, Li Zhang, Xuejin Gao, Xinying Wang
Compelling evidence demonstrates the crucial role of the commensal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. However, the effects of commensal microbiota on intestinal mucosa antimicrobial molecules have not been elucidated systematically. Here, we investigate the impacts of antibiotic-induced depletion and subsequent restoration of the intestinal microbiota on the murine antimicrobial molecules in intestinal mucosa. Our results demonstrate that depletion of commensal microbiota leads to intestinal mucosa atrophy and reduction of antimicrobial molecules, including lysozyme, regenerating islet-derived protein 3 gamma (RegIIIγ), and cryptdin 5 mRNA, whereas subsequent reconstitution of intestinal microbiota by fecal microbiota transplantation (FMT) rescues mucosa morphology and antimicrobials...
July 2018: Innate Immunity
Qiong-Feng Chen, Xiao-Dong Kuang, Qi-Feng Yuan, Hua Hao, Ting Zhang, Yong-Hong Huang, Xiao-Yan Zhou
Previous studies have reported that lipoxin A4 (LXA4) and the angiotensin I-converting enzyme 2 (ACE2), angiotensin-(1-7) [Ang-(1-7)], and its receptor Mas [ACE2-Ang-(1-7)-Mas] axis play important protective roles in acute lung injury (ALI). However, there is still no direct evidence of LXA4-mediated protection via the ACE2-Ang-(1-7)-Mas axis during ALI. This work was performed using an LPS-induced ALI mouse model and the data indicated the following. First, the animal model was established successfully and LXA4 ameliorated LPS-induced ALI...
July 2018: Innate Immunity
Junhui He, Mingchong Sun, Sujian Tian
Lupus nephritis (LN) is a multifactorial event that contributes to the long-term mortality of systemic lupus erythematosus (SLE). Activation of NLRP3 inflammasome has been known to play a role in SLE pathogenesis. We evaluated the renal protection effects of procyanidin B2 (PCB2) and the involvement of NLRP3 in a mouse model involving MRL/lpr and MRL/MpJ mice. Kidney injury was evaluated by measuring the renal clinical and pathological features, renal immune complex deposition, and serum anti-double-stranded (anti-dsDNA) Abs...
July 2018: Innate Immunity
Yohei Takeda, Masahiro Azuma, Ryoko Hatsugai, Yukari Fujimoto, Masahito Hashimoto, Koichi Fukase, Misako Matsumoto, Tsukasa Seya
The TLR2 agonist, dipalmitoyl lipopeptide (Pam2LP), has been used as an immune adjuvant without much success. Pam2LP is recognised by TLR2/6 receptors in humans and in mice. This study examined the proliferative activity of cytotoxic T lymphocytes (CTL) using mouse Ag-presenting dendritic cells (DCs) and OT-I assay system, where a library of synthetic Pam2LP was utilised from the Staphylococcus aureus database. Ag-specific CTL expansion and IFN-γ levels largely depended on the Pam2LP peptide sequence. The first Aa is cysteine (Cys), which has an active SH residue to bridge fatty acids, and the second and third Aa are hydrophilic or non-polar...
July 2018: Innate Immunity
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