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Mucosal Immunology

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https://www.readbyqxmd.com/read/28537249/airway-t-cells-protect-against-rsv-infection-in-the-absence-of-antibody
#1
E Kinnear, L Lambert, J U McDonald, H M Cheeseman, L J Caproni, J S Tregoning
Tissue resident memory T (Trm) cells act as sentinels and early responders to infection. Respiratory syncytial virus (RSV)-specific Trm cells have been detected in the lungs after human RSV infection, but whether they have a protective role is unknown. To dissect the protective function of Trm cells, BALB/c mice were infected with RSV; infected mice developed antigen-specific CD8(+) Trm cells (CD103(+)/CD69(+)) in the lungs and airways. Intranasally transferring cells from the airways of previously infected animals to naïve animals reduced weight loss on infection in the recipient mice...
May 24, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28513596/an-innate-defense-peptide-bpifa1-splunc1-restricts-influenza-a-virus-infection
#2
K M Akram, N A Moyo, G H Leeming, L Bingle, S Jasim, S Hussain, A Schorlemmer, A Kipar, P Digard, R A Tripp, R V Shohet, C D Bingle, J P Stewart
The airway epithelium secretes proteins that function in innate defense against infection. Bactericidal/permeability-increasing fold-containing family member A1 (BPIFA1) is secreted into airways and has a protective role during bacterial infections, but it is not known whether it also has an antiviral role. To determine a role in host defense against influenza A virus (IAV) infection and to find the underlying defense mechanism, we developed transgenic mouse models that are deficient in BPIFA1 and used these, in combination with in vitro three-dimensional mouse tracheal epithelial cell (mTEC) cultures, to investigate its antiviral properties...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28513595/hiv-2-infection-is-associated-with-preserved-galt-homeostasis-and-epithelial-integrity-despite-ongoing-mucosal-viral-replication
#3
S M Fernandes, A R Pires, P Matoso, C Ferreira, H Nunes-Cabaço, L Correia, E Valadas, J Poças, P Pacheco, H Veiga-Fernandes, R B Foxall, A E Sousa
The mechanisms that enable preservation of gut mucosal integrity during persistent viral replication and inherent inflammation remain unclear. Here, we investigated, for the first time, gut homeostasis in HIV-2 infection, a naturally occurring form of attenuated HIV disease. We found viral replication in both sigmoid and ileum of asymptomatic HIV-2+ patients (range: 240-851 circulating CD4+T-cells per μl) despite their undetectable viremia, accompanied by interferon-γ-producing CD8 T-cell expansion, irrespective of antiretroviral treatment...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28513594/regionally-compartmentalized-resident-memory-t-cells-mediate-naturally-acquired-protection-against-pneumococcal-pneumonia
#4
N Ms Smith, G A Wasserman, F T Coleman, K L Hilliard, K Yamamoto, E Lipsitz, R Malley, H Dooms, M R Jones, L J Quinton, J P Mizgerd
As children age, they become less susceptible to the diverse microbes causing pneumonia. These microbes are pathobionts that infect the respiratory tract multiple times during childhood, generating immunological memory. To elucidate mechanisms of such naturally acquired immune protection against pneumonia, we modeled a relevant immunological history in mice by infecting their airways with mismatched serotypes of Streptococcus pneumoniae (pneumococcus). Previous pneumococcal infections provided protection against a heterotypic, highly virulent pneumococcus, as evidenced by reduced bacterial burdens and long-term sterilizing immunity...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28513593/jak3-deficiency-blocks-innate-lymphoid-cell-development
#5
M L Robinette, M Cella, J B Telliez, T K Ulland, A D Barrow, K Capuder, S Gilfillan, L-L Lin, L D Notarangelo, M Colonna
Loss-of-function mutations in the tyrosine kinase JAK3 cause autosomal recessive severe combined immunodeficiency (SCID). Defects in this form of SCID are restricted to the immune system, which led to the development of immunosuppressive JAK inhibitors. We find that the B6.Cg-Nr1d1(tm1Ven)/LazJ mouse line purchased from Jackson Laboratories harbors a spontaneous mutation in Jak3, generating a SCID phenotype and an inability to generate antigen-independent professional cytokine-producing innate lymphoid cells (ILCs)...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28513592/ifn-%C3%AE-increases-susceptibility-to-influenza-a-infection-through-suppression-of-group-ii-innate-lymphoid-cells
#6
D Califano, Y Furuya, S Roberts, D Avram, A N J McKenzie, D W Metzger
Increased levels of interferon-γ (IFN-γ) are routinely observed in the respiratory tract following influenza virus infection, yet its potential role remains unclear. We now demonstrate that influenza-induced IFN-γ restricts protective innate lymphoid cell group II (ILC2) function in the lung following challenge with the pandemic H1N1 A/CA/04/2009 (CA04) influenza virus. Specifically, IFN-γ deficiency resulted in enhanced ILC2 activity, characterized by increased production of interleukin (IL)-5 and amphiregulin, and improved tissue integrity, yet no change in ILC2 numbers, viral load or clearance...
May 17, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28488693/icos-protects-against-mortality-from-acute-lung-injury-through-activation-of-il-5-ilc2s
#7
C L Hrusch, S T Manns, D Bryazka, J Casaos, C A Bonham, M R Jaffery, K M Blaine, K A M Mills, P A Verhoef, A O Adegunsoye, J W Williams, M Y Tjota, T V Moore, M E Strek, I Noth, A I Sperling
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreversible lung scarring and loss of pulmonary function. IPF Patients suffer from a high rate of pulmonary infections and acute exacerbations of disease that further contribute to pulmonary decline. Low expression of the inducible T-cell costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts decreased survival of IPF patients, but the mechanisms by which ICOS protects are unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now demonstrate that ICOS expression enhances survival from lung injury rather than regulating fibrogenesis...
May 10, 2017: Mucosal Immunology
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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