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Mucosal Immunology

J M Greene, P Dash, S Roy, C McMurtrey, W Awad, J S Reed, K B Hammond, S Abdulhaqq, H L Wu, B J Burwitz, B F Roth, D W Morrow, J C Ford, G Xu, J Y Bae, H Crank, A W Legasse, T H Dang, H Y Greenaway, M Kurniawan, M C Gold, M J Harriff, D A Lewinsohn, B S Park, M K Axthelm, J J Stanton, S G Hansen, L J Picker, V Venturi, W Hildebrand, P G Thomas, D M Lewinsohn, E J Adams, J B Sacha
Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to a lack of macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues are conserved between human and multiple NHP species, three T-cell receptor contact-residue mutations in NHP MR1 diminish binding of human MR1 tetramers to macaque MAITs. Construction of naturally loaded macaque MR1 tetramers facilitated identification and characterization of macaque MR1-binding ligands and MAITs, both of which mirrored their human counterparts...
October 19, 2016: Mucosal Immunology
A J Byrne, M Weiss, S A Mathie, S A Walker, H L Eames, D Saliba, C M Lloyd, I A Udalova
Interferon regulatory factor 5 (IRF5) is a key transcription factor involved in the control of the expression of proinflammatory cytokine and responses to infection, but its role in regulating pulmonary immune responses to allergen is unknown. We used genetic ablation, adenoviral vector-driven overexpression, and adoptive transfer approaches to interrogate the role of IRF5 in pulmonary immunity and during challenge with the aeroallergen, house dust mite. Global IRF5 deficiency resulted in impaired lung function and extracellular matrix (ECM) deposition...
October 19, 2016: Mucosal Immunology
N M Scott, J F Lauzon-Joset, A C Jones, K T Mincham, N M Troy, J Leffler, M Serralha, S L Prescott, S A Robertson, C Pasquali, A Bosco, P G Holt, D H Strickland
Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction and/or miscarriage. Treatment strategies for protection of at-risk mothers are limited to a narrow range of vaccines, which do not cover the bulk of the common pathogens most frequently encountered. Using mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85), currently used clinically for attenuation of infection-associated airway inflammatory symptoms in infants-adults, markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial lipopolysaccharide or influenza...
October 19, 2016: Mucosal Immunology
A Sheih, W C Parks, S F Ziegler
Airway epithelial cells are among the first to encounter inhaled allergens and can initiate allergic responses by producing pro-Th2 innate cytokines. In this study, we investigated the role of epithelial-derived cytokines in sensitization to a clinically relevant allergen, cockroach allergen (CRA). Among the epithelial-derived cytokines, granulocyte macrophage colony-stimulating factor (GM-CSF) had a central role in the initiation of Th2 allergic responses to CRA. We show that initial exposure to CRA directly activated airway epithelial cells through a TLR4-MyD88-dependent pathway and MyD88 signaling in epithelial cells induced upregulation of GM-CSF during sensitization...
October 12, 2016: Mucosal Immunology
S Kang, C Zhang, T Ohno, M Azuma
The PD-1/B7-H1 pathway regulates immune responses and maintains homeostasis. Here, we identified a unique expression of B7 homolog 1 (B7-H1) on masticatory mucosae in the oral cavity. B7-H1 was physiologically expressed on the dorsal surface of the tongue, gingiva, and hard palate. Other squamous epithelia and other structures of the epithelia did not express B7-H1 in the steady state. Physiological B7-H1 expression on masticatory mucosae was limited on prickle cells, and its expression on basal keratinocytes (KCs) was strictly regulated...
October 12, 2016: Mucosal Immunology
L Mascarell, S Airouche, N Berjont, C Gary, C Gueguen, G Fourcade, B Bellier, D Togbe, B Ryffel, D Klatzmann, V Baron-Bodo, P Moingeon
The complement subunit C1q was recently identified as a marker for monocyte-derived regulatory dendritic cells supporting the differentiation of interleukin (IL)-10-secreting CD4(+) T cells with a suppressive activity. Furthermore, C1q expression is upregulated in peripheral blood mononuclear cells of allergic patients in the course of successful allergen immunotherapy. Herein, we investigated a potential direct role of C1q in downregulating allergic inflammation. In mice with ovalbumin (OVA) or birch pollen (BP)-induced allergic asthma, C1q is as efficacious as dexamethasone to reduce both airway hyperresponsiveness (AHR), eosinophil, and ILC2 infiltrates in bronchoalveolar lavages, as well as allergen-specific T helper 2 cells in the lungs...
October 12, 2016: Mucosal Immunology
T G Coursey, F Bian, M Zaheer, S C Pflugfelder, E A Volpe, C S de Paiva
In both humans and animal models, the development of Sjögren syndrome (SS) and non-SS keratoconjunctivitis sicca (KCS) increases with age. Here, we investigated the ocular surface and lacrimal gland (LG) phenotype of NOD.B10.H2(b) mice at 7-14, 45-50, and 96-100 weeks. Aged mice develop increased corneal permeability, CD4(+) T-cell infiltration, and conjunctival goblet cell loss. Aged mice have LG atrophy with increased lymphocyte infiltration and inflammatory cytokine levels. An increase in the frequency of CD4(+)Foxp3(+) T regulatory cells (Tregs) was observed with age in the cervical lymph node (CLN), spleen, and LG...
October 5, 2016: Mucosal Immunology
L Li, J Tu, Y Jiang, J Zhou, D J Schust
Pregnancy loss is the commonest complication of pregnancy. The causes of pregnancy loss are poorly understood. It has been reported that stimulation of invariant natural killer T (iNKT) cells using α-galactosylceramide (αGC) induces pregnancy loss in mice. Here we investigated the mechanisms, especially the role of regulatory T (Treg) cells, in iNKT cell-mediated pregnancy loss. We found that injection of αGC rapidly induced fetal resorption, activated decidual iNKT cells, decreased the percentage of decidual Treg cells and their interleukin (IL)-10 and transforming growth factor (TGF)-β production, and upregulated the levels of interferon (IFN)-γ, tumor necrosis factor-α, IL-4, and IL-10 in serum...
October 5, 2016: Mucosal Immunology
G Eberl
RORγt is a nuclear hormone receptor that has followed an exponential success carrier. Its modest origins as an orphan receptor cloned from human pancreas blossomed within 15 years into a critical regulator of anti-microbial immunity and a major target in the fight against inflammatory pathologies. Here, I review its role as a transcription factor required for the generation of type 3 lymphoid cells, which induce the development of lymphoid tissues, provide resistance of epithelial stem cells to injury, maintain homeostasis with the symbiotic microbiota, orchestrate defense against extracellular microbes, and regulate allergic responses...
October 5, 2016: Mucosal Immunology
B R Leaker, V A Malkov, R Mogg, M K Ruddy, G C Nicholson, A J Tan, C Tribouley, G Chen, I De Lepeleire, N A Calder, H Chung, P Lavender, L N Carayannopoulos, T T Hansel
Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1β), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples...
September 28, 2016: Mucosal Immunology
N Torow, B J Marsland, M W Hornef, E S Gollwitzer
Although largely deprived from exogenous stimuli in utero, the mucosal barriers of the neonate after birth are bombarded by environmental, nutritional, and microbial exposures. The microbiome is established concurrently with the developing immune system. The nature and timing of discrete interactions between these two factors underpins the long-term immune characteristics of these organs, and can set an individual on a trajectory towards or away from disease. Microbial exposures in the gastrointestinal and respiratory tracts are some of the key determinants of the overall immune tone at these mucosal barriers and represent a leading target for future intervention strategies...
September 21, 2016: Mucosal Immunology
Y Qiu, J Guo, R Mao, K Chao, B-L Chen, Y He, Z-R Zeng, S-H Zhang, M-H Chen
Toll-like receptor-3 (TLR3) priming may enhance mesenchymal stem cell (MSC) immunosuppressive activity, but this mechanism has not been investigated in the context of inflammatory bowel disease. Thus, we assessed the immunosuppressive properties of TLR3-primed MSCs using a trinitrobenzene sulfonate (TNBS)-induced mouse model of colitis. Intraperitoneally injected polyribocytidylic acid (poly (I:C)- (a ligand of TLR3) primed human umbilical cord-derived MSCs (hUC-MSCs) migrated to the inflamed colon and effectively improved clinical and pathological manifestations in colitic mice compared with mice treated with unstimulated hUC-MSCs (UCMs)...
September 21, 2016: Mucosal Immunology
K L Flannigan, V L Ngo, D Geem, A Harusato, S A Hirota, C A Parkos, N W Lukacs, A Nusrat, V Gaboriau-Routhiau, N Cerf-Bensussan, A T Gewirtz, T L Denning
Specific components of the intestinal microbiota are capable of influencing immune responses such that a mutualistic relationship is established. In mice, colonization with segmented filamentous bacteria (SFB) induces T-helper-17 (Th17) cell differentiation in the intestine, yet the effector functions of interleukin (IL)-17A in response to SFB remain incompletely understood. Here we report that colonization of mice with SFB-containing microbiota induced IL-17A- and CXCR2-dependent recruitment of neutrophils to the ileum...
September 14, 2016: Mucosal Immunology
M A Pallett, V F Crepin, N Serafini, M Habibzay, O Kotik, J Sanchez-Garrido, J P Di Santo, A R Shenoy, C N Berger, G Frankel
The human pathogen enteropathogenic Escherichia coli (EPEC), as well as the mouse pathogen Citrobacter rodentium, colonize the gut mucosa via attaching and effacing lesion formation and cause diarrheal diseases. EPEC and C. rodentium type III secretion system (T3SS) effectors repress innate immune responses and infiltration of immune cells. Inflammatory caspases such as caspase-1 and caspase-4/11 are crucial mediators of host defense and inflammation in the gut via their ability to process cytokines such as interleukin (IL)-1β and IL-18...
September 14, 2016: Mucosal Immunology
H J Min, J-H Kim, J E Yoo, J-H Oh, K S Kim, J-H Yoon, C-H Kim
High-mobility group box 1 (HMGB1) mediates various functions according to the location. We tried to investigate the role of HMGB1 in upper airway under hypoxic conditions. We cultured primary normal human nasal epithelium (NHNE) cells under hypoxic conditions and evaluated the movement of HMGB1 by western blotting, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) level was evaluated to estimate the translocation mechanism of HMGB1. The role of secreted HMGB1 was evaluated by ELISA assay...
September 14, 2016: Mucosal Immunology
T Sun, O L Rojas, C Li, L A Ward, D J Philpott, J L Gommerman
Although we know a great deal about which types of dendritic cells (DCs) promote T-cell priming in the periphery, less is known about which DC subset(s) provoke antiviral responses within the gut. Here we report that conventional Zbtb46-dependent DCs were critically required for antiviral CD8(+) T-cell responses against rotavirus (RV), the major cause of childhood gastroenteritis worldwide. Furthermore, we found that in adult mice, Batf3-dependent DCs were required for generating optimal RV-specific CD8(+) T-cell responses...
September 7, 2016: Mucosal Immunology
M A van Leeuwen, L M M Costes, L A van Berkel, Y Simons-Oosterhuis, M F du Pré, A E Kozijn, H C Raatgeep, D J Lindenbergh-Kortleve, N van Rooijen, F Koning, J N Samsom
Celiac disease is caused by inflammatory T-cell responses against the insoluble dietary protein gliadin. We have shown that, in humanized mice, oral tolerance to deamidated chymotrypsin-digested gliadin (CT-TG2-gliadin) is driven by tolerogenic interferon (IFN)-γ- and interleukin (IL)-10-secreting type 1 regulatory T-like cells (Tr1-like cells) generated in the spleen but not in the mesenteric lymph nodes. We aimed to uncover the mechanisms underlying gliadin-specific Tr1-like-cell differentiation and hypothesized that proteolytic gliadin degradation by splenic macrophages is a decisive step in this process...
August 31, 2016: Mucosal Immunology
E Mitsi, A M Roche, J Reiné, T Zangari, J T Owugha, S H Pennington, J F Gritzfeld, A D Wright, A M Collins, S van Selm, M I de Jonge, S B Gordon, J N Weiser, D M Ferreira
The ability of pneumococcal conjugate vaccine (PCV) to decrease transmission by blocking the acquisition of colonization has been attributed to herd immunity. We describe the role of mucosal immunoglobulin G (IgG) to capsular polysaccharide (CPS) in mediating protection from carriage, translating our findings from a murine model to humans. We used a flow cytometric assay to quantify antibody-mediated agglutination demonstrating that hyperimmune sera generated against an unencapsulated mutant was poorly agglutinating...
August 31, 2016: Mucosal Immunology
M Rodriguez-Garcia, Z Shen, F D Barr, A W Boesch, M E Ackerman, J C Kappes, C Ochsenbauer, C R Wira
Dendritic cells (DCs) throughout the female reproductive tract (FRT) were examined for phenotype, HIV capture ability and innate anti-HIV responses. Two main CD11c(+) DC subsets were identified: CD11b(+) and CD11b(low) DCs. CD11b(+)CD14(+) DCs were the most abundant throughout the tract. A majority of CD11c(+)CD14(+) cells corresponded to CD1c(+) myeloid DCs, whereas the rest lacked CD1c and CD163 expression (macrophage marker) and may represent monocyte-derived cells. In addition, we identified CD103(+) DCs, located exclusively in the endometrium, whereas DC-SIGN(+) DCs were broadly distributed throughout the FRT...
August 31, 2016: Mucosal Immunology
J-C Ryu, M-J Kim, Y Kwon, J-H Oh, S S Yoon, S J Shin, J-H Yoon, J-H Ryu
Nod-like receptor family, CARD domain-containing 4 (NLRC4) inflammasome activation is required for efficient clearance of intracellular pathogens through caspsase-1-dependent pyroptosis in macrophages. Although neutrophils have a critical role in protection from Pseudomonas aeruginosa infection, the mechanisms regulating inflammasome-mediated pyroptosis in neutrophils and its physiological role are largely unknown. We sought to determine the specific mechanisms regulating neutrophil pyroptosis in P. aeruginosa strain PAO1 (PAO1) lung infection and to identify the pathological role of this process...
August 24, 2016: Mucosal Immunology
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