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Mucosal Immunology

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https://www.readbyqxmd.com/read/29297502/immunity-to-gastrointestinal-nematode-infections
#1
REVIEW
D Sorobetea, M Svensson-Frej, R Grencis
Numerous species of nematodes have evolved to inhabit the gastrointestinal tract of animals and humans, with over a billion of the world's population infected with at least one species. These large multicellular pathogens present a considerable and complex challenge to the host immune system given that individuals are continually exposed to infective stages, as well as the high prevalence in endemic areas. This review summarizes our current understanding of host-parasite interactions, detailing induction of protective immunity, mechanisms of resistance, and resolution of the response...
January 3, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29297501/t-bet-independent-th1-response-induces-intestinal-immunopathology-during-toxoplasma-gondii-infection
#2
Américo H López-Yglesias, Elise Burger, Alessandra Araujo, Andrew T Martin, Felix Yarovinsky
Coordinated production of IFN-γ by innate and adaptive immune cells is central for host defense, but can also trigger immunopathology. The investigation of the lymphoid cell-specific contribution to the IFN-γ-mediated intestinal pathology during Toxoplasma gondii infection identified CD4+ T cells as a key cell population responsible for IFN-γ-dependent intestinal inflammation and Paneth cell loss, where T-bet-dependent group 1 innate lymphoid cells have a minor role in driving the parasite-induced immunopathology...
January 3, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29297500/oral-gut-connection-one-step-closer-to-an-integrated-view-of-the-gastrointestinal-tract
#3
R Lira-Junior, E A Boström
Although an enrichment of orally derived bacteria is reported in the gut microbiota of patients with several diseases, it is mostly unknown whether oral bacteria can colonize and induce intestinal inflammation. In a recent paper in Science, Atarashi et al.1 from Kenya Honda's laboratory show that a subset of orally derived bacteria colonizes and persists in the gut, leading to activation of the intestinal immune system and subsequent chronic inflammation in a susceptible host. The impact of oral health status as a potential contributor to inflammatory diseases at distal sites of the body deserves consideration...
January 3, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29297499/differential-regulation-of-the-transcriptomic-and-secretomic-landscape-of-sensor-and-effector-functions-of-human-airway-epithelial-cells
#4
Roland Lehmann, Mario M Müller, Tilman E Klassert, Dominik Driesch, Magdalena Stock, Anina Heinrich, Theresia Conrad, Christoph Moore, Uta K Schier, Reinhard Guthke, Hortense Slevogt
Protein secretion upon TLR, TNFR1, and IFNGR ligation in the human airways is considered to be central for the orchestration of pulmonary inflammatory and immune responses. In this study, we compared the gene expression and protein secretion profiles in response to specific stimulation of all expressed TLRs and in further comparison to TNFR1 and IFNGR in primary human airway epithelial cells. In addition to 22 cytokines, we observed the receptor-induced regulation of 571 genes and 1,012 secreted proteins. Further analysis revealed high similarities between the transcriptional TLR sensor and TNFR1 effector responses...
January 3, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29297498/epithelial-hes1-maintains-gut-homeostasis-by-preventing-microbial-dysbiosis
#5
X-K Guo, J Ou, S Liang, X Zhou, X Hu
Recent advancements suggest that in addition to its roles in developmental processes, transcription repressor hairy and enhancer of split 1 (Hes1) also acts as a key regulator of inflammatory responses. A healthy gut microbiota ecology is critical for establishment of tissue homeostasis. However, the role of epithelial Hes1 in regulating intestinal microbiota ecology and intestinal homeostasis remains unexplored. Here we show that epithelial Hes1 deficiency leads to intestinal microbial dysbiosis and disturbed homeostasis...
January 3, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29346350/epithelial-mesenchymal-transition-in-crohn-s-disease
#6
REVIEW
H Jiang, J Shen, Z Ran
Crohn's disease (CD) is often accompanied by the complications of intestinal strictures and fistulas. These complications remain obstacles in CD treatment. In recent years, the importance of epithelial-mesenchymal transition in the pathogenesis of CD-associated fistulas and intestinal fibrosis has become apparent. Epithelial-mesenchymal transition refers to a dynamic change, wherein epithelial cells lose their polarity and adherence and acquire migratory function and fibroblast features. During formation of CD-associated fistulas, intestinal epithelial cells dislocate from the basement membrane and migrate to the lining of the fistula tracts, where they convert into transitional cells as a compensatory response under the insufficient wound healing condition...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29346349/early-treatment-of-siv-macaques-with-an-%C3%AE-4%C3%AE-7-mab-alters-virus-distribution-and-preserves-cd4-t-cells-in-later-stages-of-infection
#7
P J Santangelo, C Cicala, S N Byrareddy, K T Ortiz, D Little, K E Lindsay, S Gumber, J J Hong, K Jelicic, K A Rogers, C Zurla, F Villinger, A A Ansari, A S Fauci, J Arthos
Integrin α4β7 mediates the trafficking of leukocytes, including CD4+ T cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is implicated in HIV and SIV mediated chronic immune activation and leads to irreversible damage to the immune system. We employed an immuno-PET/CT imaging technique to evaluate the impact of an anti-integrin α4β7 mAb alone or in combination with ART, on the distribution of both SIV infected cells and CD4+ cells in rhesus macaques infected with SIV. We determined that α4β7 mAb reduced viral antigen in an array of tissues of the lung, spleen, axillary, and inguinal lymph nodes...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29346348/macrophages-regulate-lung-ilc2-activation-via-pla2g5-dependent-mechanisms
#8
M Yamaguchi, S K Samuchiwal, O Quehenberger, J A Boyce, B Balestrieri
Group V phospholipase A2 (Pla2g5) is a lipid-generating enzyme necessary for macrophage effector functions in pulmonary inflammation. However, the lipid mediators involved and their cellular targets have not been identified. Mice lacking Pla2g5 showed markedly reduced lung ILC2 activation and eosinophilia following repetitive Alternaria Alternata inhalation. While Pla2g5-null mice had Wt levels of immediate IL-33 release after one Alternaria dose, they failed to upregulate IL-33 in macrophages following repeated Alternaria administration...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29346347/cd103-cd11b-mucosal-classical-dendritic-cells-initiate-long-term-switched-antibody-responses-to-flagellin
#9
A Flores-Langarica, K Müller Luda, E K Persson, C N Cook, S Bobat, J L Marshall, M W Dahlgren, K Hägerbrand, K M Toellner, M D Goodall, D R Withers, I R Henderson, B Johansson Lindbom, A F Cunningham, W W Agace
Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103+CD11b+ (DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+CD11b- (SP) are not required for these responses...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29346346/protein-kinase-c-delta-pkc%C3%AE-a-marker-of-inflammation-and-tuberculosis-disease-progression-in-humans-is-important-for-optimal-macrophage-killing-effector-functions-and-survival-in-mice
#10
S P Parihar, M Ozturk, M J Marakalala, D T Loots, R Hurdayal, D Beukes, M Van Reenen, D E Zak, S K Mbandi, F Darboe, A Penn-Nicholson, W A Hanekom, M Leitges, T J Scriba, R Guler, F Brombacher
This corrects the article DOI: 10.1038/mi.2017.68.
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29346345/the-cytosolic-sensor-sting-is-required-for-intestinal-homeostasis-and-control-of-inflammation
#11
M C C Canesso, L Lemos, T C Neves, F M Marim, T B R Castro, É S Veloso, C P Queiroz, J Ahn, H C Santiago, F S Martins, J Alves-Silva, E Ferreira, D C Cara, A T Vieira, G N Barber, S C Oliveira, A M C Faria
STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING-/- mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29346344/development-of-immune-and-microbial-environments-is-independently-regulated-in-the-mammary-gland
#12
K Niimi, K Usami, Y Fujita, M Abe, M Furukawa, Y Suyama, Y Sakai, M Kamioka, N Shibata, E J Park, S Sato, H Kiyono, H Yoneyama, H Kitazawa, K Watanabe, T Nochi, H Aso
Breastfeeding is important for mammals, providing immunological and microbiological advantages to neonates, together with the nutritional supply from the mother. However, the mechanisms of this functional diversity in the mammary gland remain poorly characterized. Here, we show that, similar to the gastrointestinal tract, the mammary gland develops immune and microbial environments consisting of immunoglobulin A (IgA) and the microflora, respectively, both of which are important for protecting neonates and the mother from infectious diseases...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29210363/inos-and-nox1-dependent-ros-production-maintains-bacterial-homeostasis-in-the-ileum-of-mice
#13
C Matziouridou, S D C Rocha, O A Haabeth, K Rudi, H Carlsen, A Kielland
The intestinal epithelial cells constitute the first line of defense against gut microbes, which includes secretion of various antimicrobial substances. Reactive oxygen species (ROS) are well characterized as part of the innate phagocytic immunity; however, a role in controlling microorganisms in the gut lumen is less clear. Here, we show a role for nitric oxide synthase (iNOS)- and NOX1-produced ROS in maintaining homeostasis of the gut microbiota. In vivo imaging revealed distinctly high levels of ROS in the ileum of normal healthy mice, regulated in accordance with the amount of gut bacteria...
December 6, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29186109/absence-of-specific-alternatively-spliced-exon-of-cd44-in-macrophages-prevents-colitis
#14
B M Wittig, R Sabat, P Holzlöhner, E Witte-Händel, K Heilmann, K Witte, J Triebus, A Tzankov, J D Laman, B Bokemeyer, L Terracciano, C Schwärzler, H Kohler, R Volkmer, C Loddenkemper, K Wolk, U Hoffmann, U Günthert
CD44 is a transmembrane molecule appearing in numerous isoforms generated by insertions of alternatively spliced variant exons (CD44v) and having various binding partners. CD44v7 on T cells was proposed to promote colitis by preventing T-cell apoptosis. Here we demonstrate that Cd44v7-deficient T cells - like Cd44 wild-type (Cd44WT) T cells - provoked disease in two different colitis models: the model induced by CD4+CD45RBhigh T-cell transfer into Rag2-deficient mice and a new model based on ovalbumin (OVA)-specific T-cell transfer into Rag-sufficient, OVA-challenged mice...
November 29, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29186108/il-15-supports-the-generation-of-protective-lung-resident-memory-cd4-t-cells
#15
T M Strutt, K Dhume, C M Finn, J H Hwang, C Castonguay, S L Swain, K K McKinstry
Tissue-resident memory T cells (TRM) provide optimal defense at the sites of infection, but signals regulating their development are unclear, especially for CD4 T cells. Here we identify two distinct pathways that lead to the generation of CD4 TRM in the lungs following influenza infection. The TRM are transcriptionally distinct from conventional memory CD4 T cells and share a gene signature with CD8 TRM. The CD4 TRM are superior cytokine producers compared with conventional memory cells, can protect otherwise naive mice against a lethal influenza challenge, and display functional specialization by inducing enhanced inflammatory responses from dendritic cells compared with conventional memory cells...
November 29, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29186107/mucocutaneous-il-17-immunity-in-mice-and-humans-host-defense-vs-excessive-inflammation
#16
REVIEW
J Li, J-L Casanova, A Puel
Interleukin (IL)-17A is a pro-inflammatory cytokine in mice and humans. It is recognized as a key factor for the protection of mice against various pathogens, but it also underlies pathogenic inflammatory responses in numerous mouse models. The inborn errors of IL-17A- and IL-17F-mediated immunity identified in humans in the last decade have revealed that IL-17A and IL-17F are key players in mucocutaneous immunity to Candida albicans, and, to a lesser extent, Staphylococcus aureus. By contrast, there is currently no genetic evidence for a causal link between excess of IL-17 and autoimmunity, autoinflammation, or allergy in humans...
November 29, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29139478/trigger-happy-resident-memory-cd4-t-cells-inhabit-the-human-lungs
#17
A E Oja, B Piet, C Helbig, R Stark, D van der Zwan, H Blaauwgeers, E B M Remmerswaal, D Amsen, R E Jonkers, P D Moerland, M A Nolte, R A W van Lier, P Hombrink
Resident memory T cells (TRM) reside in the lung epithelium and mediate protective immunity against respiratory pathogens. Although lung CD8+ TRM have been extensively characterized, the properties of CD4+ TRM remain unclear. Here we determined the transcriptional signature of CD4+ TRM, identified by the expression of CD103, retrieved from human lung resection material. Various tissue homing molecules were specifically upregulated on CD4+ TRM, whereas expression of tissue egress and lymph node homing molecules were low...
November 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29139477/a-dietary-flavone-confers-communicable-protection-against-colitis-through-nlrp6-signaling-independently-of-inflammasome-activation
#18
K Radulovic, S Normand, A Rehman, A Delanoye-Crespin, J Chatagnon, M Delacre, N Waldschmitt, L F Poulin, J Iovanna, B Ryffel, P Rosenstiel, M Chamaillard
Flavones represent a class of polyphenols that are found in many plant-derived food sources. Herein, we provide evidence that the anti-inflammatory and antiproliferative effect of the flavone apigenin relies on the regulation of the gut microbiota by the NOD-like receptor family pyrin domain containing 6 (Nlrp6). When challenged by dextran sulfate sodium (DSS) in drinking water, mice were protected against colitis upon cohousing with apigenin-treated animals. In contrast, the protective effect was lost in the absence of Nlrp6...
November 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29139476/detection-of-hiv-1-specific-gastrointestinal-tissue-resident-cd8-t-cells-in-chronic-infection
#19
Brenna E Kiniry, Shengbin Li, Anupama Ganesh, Peter W Hunt, Ma Somsouk, Pamela J Skinner, Steven G Deeks, Barbara L Shacklett
Tissue-resident memory (TRM) CD8(+) T-cells are non-recirculating, long-lived cells housed in tissues that can confer protection against mucosal pathogens. Human immunodeficiency virus-1 (HIV-1) is a mucosal pathogen and the gastrointestinal tract is an important site of viral pathogenesis and transmission. Thus, CD8(+) TRM cells may be an important effector subset for controlling HIV-1 in mucosal tissues. This study sought to determine the abundance, phenotype, and functionality of CD8(+) TRM cells in the context of chronic HIV-1 infection...
November 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29139475/intestinal-epithelial-cell-specific-rar%C3%AE-depletion-results-in-aberrant-epithelial-cell-homeostasis-and-underdeveloped-immune-system
#20
H B Jijon, L Suarez-Lopez, O E Diaz, S Das, J De Calisto, M B Yaffe, M J Pittet, J R Mora, Y Belkaid, R J Xavier, E J Villablanca
Retinoic acid (RA), a dietary vitamin A metabolite, is crucial in maintaining intestinal homeostasis. RA acts on intestinal leukocytes to modulate their lineage commitment and function. Although the role of RA has been characterized in immune cells, whether intestinal epithelial cells (IECs) rely on RA signaling to exert their immune-regulatory function has not been examined. Here we demonstrate that lack of RA receptor α (RARα) signaling in IECs results in deregulated epithelial lineage specification, leading to increased numbers of goblet cells and Paneth cells...
November 15, 2017: Mucosal Immunology
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