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Mucosal Immunology

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https://www.readbyqxmd.com/read/29139478/trigger-happy-resident-memory-cd4-t-cells-inhabit-the-human-lungs
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/29091081/protective-role-of-%C3%AE-%C3%AE-t-cells-in-cigarette-smoke-and-influenza-infection
#5
M J Hong, B H Gu, M C Madison, C Landers, H Y Tung, M Kim, X Yuan, R You, A A Machado, B E Gilbert, P Soroosh, M Elloso, L Song, M Chen, D B Corry, G Diehl, F Kheradmand
Airborne pathogens commonly trigger severe respiratory failure or death in smokers with lung disease. Cigarette smoking compromises the effectiveness of innate immunity against infections but the underlying mechanisms responsible for defective acquired immune responses in smokers remains less clear. We found that mice exposed to chronic cigarette smoke recovered poorly from primary Influenza A pneumonia with reduced type I and II interferons (IFNs) and viral-specific immunoglobulins, but recruited γδ T cells to the lungs that predominantly expressed interleukin 17A (IL-17A)...
November 1, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29091080/campylobacter-jejuni-impairs-sodium-transport-and-epithelial-barrier-function-via-cytokine-release-in-human-colon
#6
R Bücker, S M Krug, V Moos, C Bojarski, M R Schweiger, M Kerick, A Fromm, S Janßen, M Fromm, N A Hering, B Siegmund, T Schneider, C Barmeyer, J D Schulzke
This corrects the article DOI: 10.1038/mi.2017.66.
November 1, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29091079/nox1-loss-of-function-genetic-variants-in-patients-with-inflammatory-bowel-disease
#7
T Schwerd, R V Bryant, S Pandey, M Capitani, L Meran, J-B Cazier, J Jung, K Mondal, M Parkes, C G Mathew, K Fiedler, D J McCarthy, P B Sullivan, A Rodrigues, S P L Travis, C Moore, J Sambrook, W H Ouwehand, D J Roberts, J Danesh, R K Russell, D C Wilson, J R Kelsen, R Cornall, L A Denson, S Kugathasan, U G Knaus, E G Serra, C A Anderson, R H Duerr, D Pb McGovern, J Cho, F Powrie, V Sw Li, A M Muise, H H Uhlig
Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p...
November 1, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29068000/%C3%AE-glucans-in-food-modify-colonic-microflora-by-inducing-antimicrobial-protein-calprotectin-in-a-dectin-1-induced-il-17f-dependent-manner
#8
T Kamiya, C Tang, M Kadoki, K Oshima, M Hattori, S Saijo, Y Adachi, N Ohno, Y Iwakura
Dectin-1 (gene symbol: Clec7a) is a receptor for β-glucans that play an important role for the host defense against fungi. Recently, we showed that Clec7a(-/-) mice are resistant against dextran sodium sulfate (DSS)-induced colitis because of regulatory T-cell population expansion in the colon. The regulatory T-cell expansion is caused by expansion of commensal Lactobacillus murinus whose growth is suppressed by an antimicrobial protein, calprotectin S100A8/A9. In this report, we showed that S100A8 was mainly produced by mouse colonic epithelial cells...
October 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29067999/myd88-dependent-dendritic-and-epithelial-cell-crosstalk-orchestrates-immune-responses-to-allergens
#9
S Y Thomas, G S Whitehead, M Takaku, J M Ward, X Xu, K Nakano, M R Lyons-Cohen, H Nakano, K M Gowdy, P A Wade, D N Cook
Sensitization to inhaled allergens is dependent on activation of conventional dendritic cells (cDCs) and on the adaptor molecule, MyD88. However, many cell types in the lung express Myd88, and it is unclear how signaling in these different cell types reprograms cDCs and leads to allergic inflammation of the airway. By combining ATAC-seq with RNA profiling, we found that MyD88 signaling in cDCs maintained open chromatin at select loci even at steady state, allowing genes to be rapidly induced during allergic sensitization...
October 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29067998/epithelial-derived-tgf-%C3%AE-1-acts-as-a-pro-viral-factor-in-the-lung-during-influenza-a-infection
#10
L Denney, W Branchett, L G Gregory, R A Oliver, C M Lloyd
Mucosal surfaces are under constant bombardment from potentially antigenic particles and so must maintain a balance between homeostasis and inappropriate immune activation and consequent pathology. Epithelial cells have a vital role orchestrating pulmonary homeostasis and defense against pathogens. TGF-β regulates an array of immune responses-both inflammatory and regulatory-however, its function is highly location- and context-dependent. We demonstrate that epithelial-derived TGF-β acts as a pro-viral factor suppressing early immune responses during influenza A infection...
October 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29067997/il-33-promotes-gastrointestinal-allergy-in-a-tslp-independent-manner
#11
H Han, F Roan, L K Johnston, D E Smith, P J Bryce, S F Ziegler
This corrects the article DOI: 10.1038/jhh.2016.61.
October 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29067996/the-survival-of-fetal-and-bone-marrow-monocyte-derived-alveolar-macrophages-is-promoted-by-cd44-and-its-interaction-with-hyaluronan
#12
Y Dong, G F T Poon, A A Arif, S S M Lee-Sayer, M Dosanjh, P Johnson
Alveolar macrophages maintain lung homeostasis by performing important roles in immunosurveillance and lung surfactant catabolism. They express high levels of CD44 and are one of the few macrophage populations that constitutively bind hyaluronan, a ligand for CD44 and component of pericellular and extracellular matrices. Using adoptive transfer experiments and a mouse model of inflammation, we found that alveolar macrophages are initially depleted after an inflammatory insult then rapidly self-renew and return to original numbers after the resolution phase...
October 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29067995/induction-of-vaginal-resident-hiv-specific-cd8-t-cells-with-mucosal-prime-boost-immunization
#13
H-X Tan, A K Wheatley, R Esterbauer, S Jegaskanda, J J Glass, D Masopust, R De Rose, S J Kent
Tissue-resident memory (TRM) CD8 T cells survey a range of non-lymphoid mucosal tissues where they rapidly mediate clearance of viral infections at the entry portals. Vaccines that establish CD8 TRM cells in the cervicovaginal mucosa hold promise for effective immunity against sexually transmitted HIV. We demonstrate that HIV-specific CD8 TRM cells can be established in the murine vaginal mucosa using a combined intranasal and intravaginal mucosal immunization with recombinant influenza-HIV vectors. Using in situ tetramer immunofluorescence microscopy, we found that this mucosally administered prime-boost immunization also resulted in the durable seeding of CD8 T cells in the frontline vaginal epithelial compartment as opposed to the vaginal submucosa...
October 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29067994/microbiome-driven-allergic-lung-inflammation-is-ameliorated-by-short-chain-fatty-acids
#14
A Cait, M R Hughes, F Antignano, J Cait, P A Dimitriu, K R Maas, L A Reynolds, L Hacker, J Mohr, B B Finlay, C Zaph, K M McNagny, W W Mohn
The mammalian gastrointestinal tract harbors a microbial community with metabolic activity critical for host health, including metabolites that can modulate effector functions of immune cells. Mice treated with vancomycin have an altered microbiome and metabolite profile, exhibit exacerbated T helper type 2 cell (Th2) responses, and are more susceptible to allergic lung inflammation. Here we show that dietary supplementation with short-chain fatty acids (SCFAs) ameliorates this enhanced asthma susceptibility by modulating the activity of T cells and dendritic cells (DCs)...
October 25, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29044226/bone-marrow-transplant-induced-alterations-in-notch-signaling-promote-pathologic-th17-responses-to-%C3%AE-herpesvirus-infection
#15
S J Gurczynski, X Zhou, M Flaherty, C A Wilke, B B Moore
Idiopathic pneumonia syndrome (IPS) is a common, often fatal, complication following hematopoietic stem cell transplantation (HSCT) characterized by severe pneumonitis and interstitial fibrosis. Fully reconstituted syngeneic bone marrow transplant (BMT) mice infected with murine γ-herpesvirus-68 develop interleukin-17 (IL-17)-driven pneumonitis and fibrosis, which mimics clinical manifestations of IPS. We found CD103+ and CD11b+ dendritic cells (DCs) are selectively deficient for the Notch ligand, DLL4, following BMT and CD4+ T cells isolated from lungs and spleens of infected BMT mice display Notch signaling defects...
October 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28930287/exposure-to-human-alveolar-lining-fluid-enhances-mycobacterium-bovis-bcg-vaccine-efficacy-against-mycobacterium-tuberculosis-infection-in-a-cd8-t-cell-dependent-manner
#16
J I Moliva, A P Hossfeld, C H Canan, V Dwivedi, M D Wewers, G Beamer, J Turner, J B Torrelles
Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.tb) cell wall, revealing alternate antigenic epitopes on the bacterium surface that alter its pathogenicity. We hypothesized that ALF-induced modification of BCG would induce better protection against aerosol infection with M...
September 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28930286/molecular-and-cellular-signatures-underlying-superior-immunity-against-bordetella-pertussis-upon-pulmonary-vaccination
#17
R Hm Raeven, J Brummelman, J LA Pennings, L van der Maas, K Helm, W Tilstra, A van der Ark, A Sloots, P van der Ley, W van Eden, W Jiskoot, E van Riet, C Acm van Els, G Fa Kersten, W Gh Han, B Metz
Mucosal immunity is often required for protection against respiratory pathogens but the underlying cellular and molecular mechanisms of induction remain poorly understood. Here, systems vaccinology was used to identify immune signatures after pulmonary or subcutaneous immunization of mice with pertussis outer membrane vesicles. Pulmonary immunization led to improved protection, exclusively induced mucosal immunoglobulin A (IgA) and T helper type 17 (Th17) responses, and in addition evoked elevated systemic immunoglobulin G (IgG) antibody levels, IgG-producing plasma cells, memory B cells, and Th17 cells...
September 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28930285/interleukin-17a-negatively-regulates-lymphangiogenesis-in-t-helper-17-cell-mediated-inflammation
#18
H J Park, C M Yuk, K Shin, S-H Lee
During inflammation lymphatic vessels (LVs) are enlarged and their density is increased to facilitate the migration of activated immune cells and antigens. However, after antigen clearance, the expanded LVs shrink to maintain homeostasis. Here we show that interleukin (IL)-17A, secreted from T helper type 17 (TH17) cells, is a negative regulator of lymphangiogenesis during the resolution phase of TH17-mediated immune responses. Moreover, IL-17A suppresses the expression of major lymphatic markers in lymphatic endothelial cells and decreases in vitro LV formation...
September 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28853442/po-and-id-bcg-vaccination-in-humans-induce-distinct-mucosal-and-systemic-immune-responses-and-cd4-t-cell-transcriptomal-molecular-signatures
#19
D F Hoft, M Xia, G L Zhang, A Blazevic, J Tennant, C Kaplan, G Matuschak, T J Dube, H Hill, L S Schlesinger, P L Andersen, V Brusic
Protective efficacy of Bacillus Calmette-Guérin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination...
August 30, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28853441/enteroendocrine-cells-sensory-sentinels-of-the-intestinal-environment-and-orchestrators-of-mucosal-immunity
#20
REVIEW
J J Worthington, F Reimann, F M Gribble
The intestinal epithelium must balance efficient absorption of nutrients with partitioning commensals and pathogens from the bodies' largest immune system. If this crucial barrier fails, inappropriate immune responses can result in inflammatory bowel disease or chronic infection. Enteroendocrine cells represent 1% of this epithelium and have classically been studied for their detection of nutrients and release of peptide hormones to mediate digestion. Intriguingly, enteroendocrine cells are the key sensors of microbial metabolites, can release cytokines in response to pathogen associated molecules and peptide hormone receptors are expressed on numerous intestinal immune cells; thus enteroendocrine cells are uniquely equipped to be crucial and novel orchestrators of intestinal inflammation...
August 30, 2017: Mucosal Immunology
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