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Mucosal Immunology

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https://www.readbyqxmd.com/read/28443609/the-hiv-1-viral-synapse-signals-human-foreskin-keratinocytes-to-secrete-thymic-stromal-lymphopoietin-facilitating-hiv-1-foreskin-entry
#1
Z Zhou, L Xu, A Sennepin, C Federici, Y Ganor, D Tudor, D Damotte, N Barry Delongchamps, M Zerbib, M Bomsel
The complexity of signal transduction resulting from the contact of human immunodeficiency virus type 1 (HIV-1)-infected cells and mucosal cells has hampered our comprehension of HIV-1 mucosal entry. Such process is driven efficiently only by viral synapse contacts, whereas cell-free HIV-1 remains poorly infectious. Using CD4(+) T-cells expressing only HIV-1 envelope inoculated on human adult foreskin tissues, we designed methodologies to identify the signals transduced in foreskin keratinocytes following HIV-1-envelope-dependent viral synapse formation...
April 26, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28422188/resolvin-d1-enhances-the-resolution-of-lung-inflammation-caused-by-long-term-pseudomonas-aeruginosa-infection
#2
M Codagnone, E Cianci, A Lamolinara, V C Mari, A Nespoli, E Isopi, D Mattoscio, M Arita, A Bragonzi, M Iezzi, M Romano, A Recchiuti
Pseudomonas aeruginosa lung infection is a main cause of disability and mortality worldwide. Acute inflammation and its timely resolution are crucial for ensuring bacterial clearance and limiting tissue damage. Here, we investigated protective actions of resolvin (Rv) D1 in lung infection induced by the RP73 clinical strain of P. aeruginosa. RvD1 significantly diminished bacterial growth and neutrophil infiltration during acute pneumonia caused by RP73. Inoculum of RP73, immobilized in agar beads, resulted in persistent lung infection up to 21 days, leading to a non resolving inflammation reminiscent of human pathology...
April 19, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28422187/a-sphingosine-1-phosphate-receptor-1-agonist-inhibits-tertiary-lymphoid-tissue-reactivation-and-hypersensitivity-in-the-lung
#3
C A Huppé, P Blais Lecours, A Lechasseur, D R Gendron, A M Lemay, E Y Bissonnette, M R Blanchet, C Duchaine, M C Morissette, H Rosen, D Marsolais
Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P1) regulates key mechanisms underlying lymphoid tissue biology and its chemical modulation causes lymphocyte retention in lymph nodes. Given the putative immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated whether or not chemical modulation of S1P1 caused lymphocyte retention within TLTs in a model of hypersensitivity pneumonitis...
April 19, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28422186/high-fat-diet-induces-systemic-b-cell-repertoire-changes-associated-with-insulin-resistance
#4
T D Pham, M H Y Chng, K M Roskin, K J L Jackson, K D Nguyen, J Glanville, J-Y Lee, E G Engleman, S D Boyd
The development of obesity-associated insulin resistance is associated with B-lymphocyte accumulation in visceral adipose tissue (VAT) and is prevented by B-cell ablation. To characterize potentially pathogenic B-cell repertoires in this disorder, we performed high-throughput immunoglobulin (Ig) sequencing from multiple tissues of mice fed high-fat diet (HFD) and regular diet (RD). HFD significantly changed the biochemical properties of Ig heavy-chain complementarity-determining region-3 (CDRH3) sequences, selecting for IgA antibodies with shorter and more hydrophobic CDRH3 in multiple tissues...
April 19, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28401939/mdr1-deficiency-impairs-mitochondrial-homeostasis-and-promotes-intestinal-inflammation
#5
G-T Ho, R E Aird, B Liu, R K Boyapati, N A Kennedy, D A Dorward, C L Noble, T Shimizu, R N Carter, E T S Chew, N M Morton, A G Rossi, R B Sartor, J P Iredale, J Satsangi
The multidrug resistance-1 (MDR1) gene encodes an ATP-dependent efflux transporter that is highly expressed in the colon. In mice, loss of MDR1 function results in colitis with similarities to human inflammatory bowel diseases (IBD). Here, we show that MDR1 has an unexpected protective role for the mitochondria where MDR1 deficiency results in mitochondrial dysfunction with increased mitochondrial reactive oxygen species (mROS) driving the development of colitis. Exogenous induction of mROS accelerates, while inhibition attenuates colitis in vivo; these effects are amplified in MDR1 deficiency...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28401938/novel-protective-mechanism-for-interleukin-33-at-the-mucosal-barrier-during-influenza-associated-bacterial-superinfection
#6
K M Robinson, K Ramanan, M E Clay, K J McHugh, H E Rich, J F Alcorn
Influenza A is a highly contagious respiratory virus that causes seasonal epidemics and occasional worldwide pandemics. The primary cause of influenza-related mortality is bacterial superinfection. There are numerous mechanisms by which preceding influenza infection attenuates host defense, allowing for increased susceptibility to bacterial pneumonia. Herein, we demonstrate that influenza inhibits Staphylococcus aureus-induced production of interleukin-33 (IL-33). Restoration of IL-33 during influenza A and methicillin-resistant S...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28401937/progesterone-based-compounds-affect-immune-responses-and-susceptibility-to-infections-at-diverse-mucosal-sites
#7
REVIEW
Olivia J Hall, Sabra L Klein
Over 100 million women worldwide are currently on progesterone-based contraceptives to improve their health outcomes through reduced maternal mortality and family planning. In addition to their role in reproduction, progesterone-based compounds modulate immune responses throughout the body, particularly at mucosal sites. By binding to receptors located in immune cells, including natural killer cells, macrophages, dendritic cells, and T cells, as well in non-immune cells, such as epithelial and endothelial cells, progesterone-based compounds alter cellular signaling and activity to affect the outcome of infections at diverse mucosal sites, including the genital, gastrointestinal, and respiratory tracts...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28401936/bmal1-links-the-circadian-clock-to-viral-airway-pathology-and-asthma-phenotypes
#8
A Ehlers, W Xie, E Agapov, S Brown, D Steinberg, R Tidwell, G Sajol, R Schutz, R Weaver, H Yu, M Castro, L B Bacharier, X Wang, M J Holtzman, J A Haspel
Patients with asthma experience circadian variations in their symptoms. However it remains unclear how specific aspects of this common airway disease relate to clock genes, which are critical to the generation of circadian rhythms in mammals. Here, we used a viral model of acute and chronic airway disease to examine how circadian clock disruption affects asthmatic lung phenotypes. Deletion of the core clock gene bmal1 or environmental disruption of circadian function by jet lag exacerbated acute viral bronchiolitis caused by Sendai virus (SeV) and influenza A virus in mice...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28401935/unique-invariant-natural-killer-t-cells-promote-intestinal-polyps-by-suppressing-th1-immunity-and-promoting-regulatory-t-cells
#9
Y Wang, S Sedimbi, L Löfbom, A K Singh, S A Porcelli, S L Cardell
CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early regulatory cells of immune responses. Besides the established roles in the regulation of inflammation and autoimmune disease, studies have shown that iNKT cells have important roles in tumor surveillance and the control of tumor metastasis. Here we found that the absence of iNKT cells markedly decreased the total number of intestinal polyps in APC(Min/+) mice, a model for colorectal cancer. Polyp iNKT cells were enriched for interleukin-10 (IL-10)- and IL-17-producing cells, showed a distinct phenotype being CD4(+), NK1...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28401934/vaginal-lactic-acid-elicits-an-anti-inflammatory-response-from-human-cervicovaginal-epithelial-cells-and-inhibits-production-of-pro-inflammatory-mediators-associated-with-hiv-acquisition
#10
A C Hearps, D Tyssen, D Srbinovski, L Bayigga, D J D Diaz, M Aldunate, R A Cone, R Gugasyan, D J Anderson, G Tachedjian
Inflammation in the female reproductive tract (FRT) is associated with increased HIV transmission. Lactobacillus spp. dominate the vaginal microbiota of many women and their presence is associated with reduced HIV acquisition. Here we demonstrate that lactic acid (LA), a major organic acid metabolite produced by lactobacilli, mediates anti-inflammatory effects on human cervicovaginal epithelial cells. Treatment of human vaginal and cervical epithelial cell lines with LA (pH 3.9) elicited significant increases in the production of the anti-inflammatory cytokine IL-1RA...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28401933/bcl-xl-mediates-ripk3-dependent-necrosis-in-m-tuberculosis-infected-macrophages
#11
X Zhao, N Khan, H Gan, F Tzelepis, T Nishimura, S-Y Park, M Divangahi, H G Remold
Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host Mϕ, which is essential for successful pathogenesis in tuberculosis. Here we demonstrate that necrosis of Mtb-infected Mϕ is dependent on the action of the cytosolic Receptor Interacting Protein Kinase 3 (RIPK3) and the mitochondrial Bcl-2 family member protein B-cell lymphoma-extra large (Bcl-xL). RIPK3-deficient Mϕ are able to better control bacterial growth in vitro and in vivo. Mechanistically, cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and blocks caspase 8-activation and apoptosis via Bcl-xL...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28401932/inflammasomes-and-intestinal-inflammation
#12
REVIEW
N Zmora, M Levy, M Pevsner-Fischer, E Elinav
The inflammasome is a cytosolic multi-protein innate immune rheostat, sensing a variety of endogenous and environmental stimuli, and regulating homeostasis or damage control. In the gastrointestinal tract, inflammasomes orchestrate immune tolerance to microbial and potentially food-related signals or drive the initiation of inflammatory responses to invading pathogens. When inadequately regulated, intestinal inflammasome activation leads to a perpetuated inflammatory response leading to immune pathology and tissue damage...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28378808/distribution-location-and-transcriptional-profile-of-peyer-s-patch-conventional-dc-subsets-at-steady-state-and-under-tlr7-ligand-stimulation
#13
J Bonnardel, C Da Silva, C Wagner, R Bonifay, L Chasson, M Masse, E Pollet, M Dalod, J-P Gorvel, H Lelouard
The initiation of the mucosal immune response in Peyer's patch (PP) relies on the sampling, processing, and efficient presentation of foreign antigens by dendritic cells (DCs). Among PP DCs, CD11b(+) conventional DCs (cDCs) and lysozyme-expressing DCs (LysoDCs) have distinct progenitors and functions but share many cell surface markers. This has previously led to confusion between these two subsets. In addition, another PP DC subset, termed double-negative (DN), remains poorly characterized. Here we show that both DN and CD11b(+) cDCs belong to a unique SIRPα(+) cDC subset...
April 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28378807/diversity-and-functions-of-intestinal-mononuclear-phagocytes
#14
REVIEW
T Joeris, K Müller-Luda, W W Agace, A McI Mowat
The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation. In the current review we discuss the function of intestinal cDC and monocyte-derived MNP, highlighting how these subsets play several non-redundant roles in the regulation of intestinal immune responses. While much remains to be learnt, recent findings also underline how the various populations of MNP adapt to deal with the challenges specific to their environment...
April 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28378806/fibroblast-growth-factor-2-drives-and-maintains-progressive-corneal-neovascularization-following-hsv-1-infection
#15
H R Gurung, M M Carr, K Bryant, A J Chucair-Elliott, D Jj Carr
Herpes simplex virus type 1 (HSV-1) infection of the cornea induces vascular endothelial growth factor A (VEGF-A)-dependent lymphangiogenesis that continues to develop well beyond the resolution of infection. Inflammatory leukocytes infiltrate the cornea and have been implicated to be essential for corneal neovascularization, an important clinically relevant manifestation of stromal keratitis. Here we report that cornea infiltrating leukocytes including neutrophils and T cells do not have a significant role in corneal neovascularization past virus clearance...
April 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28378805/neonatal-mice-possess-two-phenotypically-and-functionally-distinct-lung-migratory-cd103-dendritic-cell-populations-following-respiratory-infection
#16
T J Ruckwardt, K M Morabito, E Bar-Haim, D Nair, B S Graham
The CD103(+) subset of lung-migratory dendritic cells (DCs) plays an important role in the generation of CD8(+) T cell responses following respiratory infection. Here, we demonstrate that the dependence on CD103(+) DCs for stimulation of RSV-specific T cells is both epitope and age-dependent. CD103(+) DCs in neonatal mice develop two phenotypically and functionally distinct populations following respiratory infection. Neonatal CD103(+) DCs expressing low levels of CD103 (CD103lo DCs) and other lineage and maturation markers including costimulatory molecules are phenotypically immature and functionally limited...
April 5, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28352104/helminth-induced-alterations-of-the-gut-microbiota-exacerbate-bacterial-colitis
#17
C Su, L Su, Y Li, S R Long, J Chang, W Zhang, W A Walker, R J Xavier, B J Cherayil, H N Shi
Infection with the intestinal helminth parasite Heligmosomoides polygyrus exacerbates the colitis caused by the bacterial enteropathogen Citrobacter rodentium. To clarify the underlying mechanism, we analyzed fecal microbiota composition of control and helminth-infected mice and evaluated the functional role of compositional differences by microbiota transplantation experiments. Our results showed that infection of Balb/c mice with H. polygyrus resulted in significant changes in the composition of the gut microbiota, characterized by a marked increase in the abundance of Bacteroidetes and decreases in Firmicutes and Lactobacillales...
March 29, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28327619/il-36%C3%AE-signaling-controls-the-induced-regulatory-t-cell-th9-cell-balance-via-nf%C3%AE%C2%BAb-activation-and-stat-transcription-factors
#18
A Harusato, H Abo, V L Ngo, S W Yi, K Mitsutake, S Osuka, J E Kohlmeier, J D Li, A T Gewirtz, A Nusrat, T L Denning
Regulatory and effector T helper (Th) cells are abundant at mucosal surfaces, especially in the intestine, where they control the critical balance between tolerance and inflammation. However, the key factors that reciprocally dictate differentiation along these specific lineages remain incompletely understood. Here we report that the interleukin-1 (IL-1) family member IL-36γ signals through IL-36 receptor, myeloid differentiation primary response gene 88, and nuclear factor-κBp50 in CD4(+) T cells to potently inhibit Foxp3-expressing induced regulatory T cell (Treg) development, while concomitantly promoting the differentiation of Th9 cells via a IL-2-STAT5- (signal transducer and activator of transcription factor 5) and IL-4-STAT6-dependent pathway...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28327618/the-transcriptional-repressor-hic1-regulates-intestinal-immune-homeostasis
#19
K Burrows, F Antignano, M Bramhall, A Chenery, S Scheer, V Korinek, T M Underhill, C Zaph
The intestine is a unique immune environment that must respond to infectious organisms but remain tolerant to commensal microbes and food antigens. However, the molecular mechanisms that regulate immune cell function in the intestine remain unclear. Here we identify the POK/ZBTB family transcription factor hypermethylated in cancer 1 (HIC1, ZBTB29) as a central component of immunity and inflammation in the intestine. HIC1 is specifically expressed in immune cells in the intestinal lamina propria (LP) in the steady state and mice with a T-cell-specific deletion of HIC1 have reduced numbers of T cells in the LP...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28327617/the-cell-surface-mucin-muc1-limits-the-severity-of-influenza-a-virus-infection
#20
J L McAuley, L Corcilius, H-X Tan, R J Payne, M A McGuckin, L E Brown
Cell surface mucin (cs-mucin) glycoproteins are constitutively expressed at the surface of respiratory epithelia where pathogens such as influenza A virus (IAV) gain entry into cells. Different members of the cs-mucin family each express a large and heavily glycosylated extracellular domain that towers above other receptors on the epithelial cell surface, a transmembrane domain that enables shedding of the extracellular domain, and a cytoplasmic tail capable of triggering signaling cascades. We hypothesized that IAV can interact with the terminal sialic acids presented on the extracellular domain of cs-mucins, resulting in modulation of infection efficiency...
March 22, 2017: Mucosal Immunology
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