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Mucosal Immunology

D Bernardo, A C Marin, S Fernández-Tomé, A Montalban-Arques, A Carrasco, E Tristán, L Ortega-Moreno, I Mora-Gutiérrez, A Díaz-Guerra, R Caminero-Fernández, P Miranda, F Casals, M Caldas, M Jiménez, S Casabona, F De la Morena, M Esteve, C Santander, M Chaparro, J P Gisbert
Although macrophages (Mϕ) maintain intestinal immune homoeostasis, there is not much available information about their subset composition, phenotype and function in the human setting. Human intestinal Mϕ (CD45+ HLA-DR+ CD14+ CD64+ ) can be divided into subsets based on the expression of CD11c, CCR2 and CX3CR1. Monocyte-like cells can be identified as CD11chigh CCR2+ CX3CR1+ cells, a phenotype also shared by circulating CD14+ monocytes. On the contrary, their Mϕ-like tissue-resident counterparts display a CD11c- CCR2- CX3CR1- phenotype...
May 9, 2018: Mucosal Immunology
Mariana X Byndloss, Sandy R Pernitzsch, Andreas J Bäumler
A balanced gut microbiota is important for human health, but the mechanisms that maintain homeostasis are incompletely understood. Recent insights suggest the host plays a key role in shaping its gut microbiota to be beneficial. While host control in the small intestine curbs bacterial numbers to avoid competition for simple sugars and amino acids, the host limits oxygen availability in the large intestine to obtain microbial fermentation products from fiber. Epithelial cells are major players in imposing ecological control mechanisms, which involves the release of antimicrobial peptides by small-intestinal Paneth cells and maintenance of luminal anaerobiosis by epithelial hypoxia in the colon...
May 9, 2018: Mucosal Immunology
Joo-Young Park, Hyunsoo Chung, Devon T DiPalma, Xuguang Tai, Jung-Hyun Park
The oral mucosa is a critical barrier tissue that protects the oral cavity against invading pathogens and foreign antigens. Interestingly, inflammation in the oral cavity is rarely observed, indicating that overt immune activation in this site is actively suppressed. Whether Foxp3+ Treg cells are involved in controlling immunity of the oral mucosa, however, is not fully understood. Here, we show that the oral mucosa is highly enriched in Foxp3+ Treg cells, and that oral mucosa Treg cells are phenotypically distinct from those of LN or spleen, as they expressed copious amounts of the tissue-retention molecule CD103 and unusually high-levels of CTLA4...
May 9, 2018: Mucosal Immunology
Mathias Schmaler, Alessia Colone, Julian Spagnuolo, Michael Zimmermann, Marco Lepore, Artem Kalinichenko, Sumedha Bhatia, Fabien Cottier, Tobias Rutishauser, Norman Pavelka, Adrian Egli, Elisa Azzali, Marco Pieroni, Gabriele Costantino, Petr Hruz, Uwe Sauer, Lucia Mori, Gennaro De Libero
Mucosal-associated invariant T (MAIT) cells are abundant innate-like T lymphocytes in mucosal tissues and recognize a variety of riboflavin-related metabolites produced by the microbial flora. Relevant issues are whether MAIT cells are heterogeneous in the colon, and whether the local environment influences microbial metabolism thereby shaping MAIT cell phenotypes and responses. We found discrete MAIT cell populations in human colon, characterized by the diverse expression of transcription factors, cytokines and surface markers, indicative of activated and precisely controlled lymphocyte populations...
May 9, 2018: Mucosal Immunology
Gabriella Aviello, Ulla G Knaus
Reactive oxygen species (ROS), initially categorized as toxic by-products of aerobic metabolism, have often been called a double-edged sword. ROS are considered indispensable when host defense and redox signaling is concerned and a threat in inflammatory or degenerative diseases. This generalization does not take in account the diversity of oxygen metabolites being generated, their physicochemical characteristics and their production by distinct enzymes in space and time. NOX/DUOX NADPH oxidases are the only enzymes solely dedicated to ROS production and the prime ROS producer for intracellular and intercellular communication due to their widespread expression and intricate regulation...
May 9, 2018: Mucosal Immunology
A Couturier-Maillard, N Froux, J Piotet-Morin, C Michaudel, L Brault, J Le Bérichel, A Sénéchal, P Robinet, P Chenuet, S Jejou, L Dumoutier, J C Renauld, J Iovanna, S Huber, Vfj Quesniaux, H Sokol, B Ryffel
Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation...
May 4, 2018: Mucosal Immunology
Jonathan C Jeschke, Christopher G Mayne, Jennifer Ziegelbauer, Christopher L DeCiantis, Selina Singh, Suresh N Kumar, Mariko Suchi, Yoichiro Iwakura, William R Drobyski, Nita H Salzman, Calvin B Williams
Homeostasis in the ileum, which is commonly disrupted in patients with Crohn's disease, involves ongoing immune responses. To study how homeostatic processes of the ileum impact CD4+ T cell responses, we used TCR transgenic tools to breed mice that spontaneously produced CD4+ T cells reactive to an antigen expressed in the ileum. At an early age, the ilea of these mice exhibit crypt hyperplasia and accumulate increased numbers of TH 17 cells bearing non-transgenic clonotypes. Half of these mice subsequently developed colitis linked to broad mucosal infiltration by TH 17 and TH 1 cells expressing non-transgenic clonotypes, chronic wasting disease and loss of ileal crypt hyperplasia...
May 4, 2018: Mucosal Immunology
Hanna Erdmann, Jochen Behrends, Kristina Ritter, Alexandra Hölscher, Johanna Volz, Ida Rosenkrands, Christoph Hölscher
During Mycobacterium tuberculosis (Mtb) infection, mice lacking the IL-27R exhibit lower bacterial burdens but develop an immunopathological sequelae in comparison to wild-type mice. We here show that this phenotype correlates with an enhanced recruitment of antigen-specific CCR6+ CD4+ T cells and an increased frequency of IL-17A-producing CD4+ T cells. By comparing the outcome of Mtb infection in C57BL/6, IL-27R-deficient and IL-27R/IL-17A-double deficient mice, we observed that both the increased protection and elevated immunopathology are supported by IL-17A...
May 4, 2018: Mucosal Immunology
Yoshinari Nakatsuka, Alexis Vandenbon, Takashi Mino, Masanori Yoshinaga, Takuya Uehata, Xiaotong Cui, Ayuko Sato, Tohru Tsujimura, Yutaka Suzuki, Atsuyasu Sato, Tomohiro Handa, Kazuo Chin, Teiji Sawa, Toyohiro Hirai, Osamu Takeuchi
Inhaled pathogens including Pseudomonas aeruginosa initially encounter airway epithelial cells (AECs), which are poised to evoke cell-intrinsic innate defense, affecting second tier of hematopoietic cell-mediated immune reaction. However, it is largely unknown how pulmonary immune responses mediated by a variety of immune cells are coordinated. Here we show that Regnase-1, an endoribonuclease expressed in AECs and immune cells, plays an essential role in coordinating innate responses and adaptive immunity against P...
April 25, 2018: Mucosal Immunology
Yu-Ling Chang, Maura Rossetti, Hera Vlamakis, David Casero, Gemalene Sunga, Nicholas Harre, Shelley Miller, Romney Humphries, Thaddeus Stappenbeck, Kenneth W Simpson, R Balfour Sartor, Gary Wu, James Lewis, Frederic Bushman, Dermot P B McGovern, Nita Salzman, James Borneman, Ramnik Xavier, Curtis Huttenhower, Jonathan Braun
Microbial metabolites are an emerging class of mediators influencing CD4+ T-cell function. To advance the understanding of direct causal microbial factors contributing to Crohn's disease, we screened 139 predicted Crohn's disease-associated microbial metabolites for their bioactivity on human CD4+ T-cell functions induced by disease-associated T helper 17 (Th17) polarizing conditions. We observed 15 metabolites with CD4+ T-cell bioactivity, 3 previously reported, and 12 unprecedented. A deeper investigation of the microbe-derived metabolite, ascorbate, revealed its selective inhibition on activated human CD4+ effector T cells, including IL-17A-, IL-4-, and IFNγ-producing cells...
April 25, 2018: Mucosal Immunology
Toufic Mayassi, Bana Jabri
The location of intraepithelial lymphocytes (IEL) between epithelial cells, their effector memory, cytolytic and inflammatory phenotype positions them to kill infected epithelial cells and protect the intestine against pathogens. Human TCRαβ+ CD8αβ+ IEL have the dual capacity to recognize modified self via natural killer (NK) receptors (autoreactivity) as well as foreign antigen via the T cell receptor (TCR), which is accomplished in mouse by two cell subsets, the naturally occurring TCRαβ+ CD8αα+ and adaptively induced TCRαβ+ CD8αβ+ IEL subsets, respectively...
April 20, 2018: Mucosal Immunology
Bruno Lamas, Jane M Natividad, Harry Sokol
Aryl hydrocarbon receptor (AhR) is a member of the basic helix-loop-helix-(bHLH) superfamily of transcription factors, which are associated with cellular responses to environmental stimuli, such as xenobiotics and oxygen levels. Unlike other members of bHLH, AhR is the only bHLH transcription factor that is known to be ligand activated. Early AhR studies focused on understanding the role of AhR in mediating the toxicity and carcinogenesis properties of the prototypic ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)...
April 7, 2018: Mucosal Immunology
D Lapuente, M Storcksdieck Genannt Bonsmann, A Maaske, V Stab, V Heinecke, K Watzstedt, R Heß, A M Westendorf, W Bayer, C Ehrhardt, M Tenbusch
A universal influenza vaccine must provide protection against antigenically divergent influenza viruses either through broadly neutralizing antibodies or cross-reactive T cells. Here, intranasal immunizations with recombinant adenoviral vectors (rAd) encoding hemagglutinin (HA) and nucleoprotein (NP) in combination with rAd-Interleukin-(IL)-1β or rAd-IL-18 were evaluated for their efficacy in BALB/c mice. Mucosal delivery of rAd-IL-1β enhanced HA-specific antibody responses including strain-specific neutralizing antibodies...
March 15, 2018: Mucosal Immunology
Yi-Lin Zhang, Peng-Xiao Chen, Wei-Jie Guan, Hong-Mei Guo, Zhuo-Er Qiu, Jia-Wen Xu, Yu-Li Luo, Chong-Feng Lan, Jian-Bang Xu, Yuan Hao, Ya-Xia Tan, Ke-Nan Ye, Zhao-Rong Lun, Lei Zhao, Yun-Xin Zhu, Jiehong Huang, Wing-Hung Ko, Wei-De Zhong, Wen-Liang Zhou, Nan-Shan Zhong
Airway epithelial cells harbor the capacity of active Cl- transepithelial transport and play critical roles in modulating innate immunity. However, whether intracellular Cl- accumulation contributes to relentless airway inflammation remains largely unclear. This study showed that, in airway epithelial cells, intracellular Cl- concentration ([Cl- ]i ) was increased after Pseudomonas aeruginosa lipopolysaccharide (LPS) stimulation via nuclear factor-κB (NF-κB)-phosphodiesterase 4D (PDE4D)-cAMP signaling pathways...
March 15, 2018: Mucosal Immunology
Manuela Hefele, Iris Stolzer, Barbara Ruder, Gui-Wei He, Mousumi Mahapatro, Stefan Wirtz, Markus F Neurath, Claudia Günther
Although induction of host cell death is a pivotal step during bacteria-induced gastroenteritis, the molecular regulation remains to be fully characterized. To expand our knowledge, we investigated the role of the central cell death regulator Caspase-8 in response to Salmonella Typhimurium. Here, we uncovered that intestinal salmonellosis was associated with strong upregulation of members of the host cell death machinery in intestinal epithelial cells (IECs) as an early event, suggesting that elimination of infected IECs represents a host defense strategy...
March 8, 2018: Mucosal Immunology
Ahmad Al-Attar, Yelena Alimova, Sreenatha Kirakodu, Anastasia Kozal, Michael John Novak, Arnold J Stromberg, Luis Orraca, Janis Gonzalez-Martinez, Melween Martinez, Jeffrey L Ebersole, Octavio A Gonzalez
P. gingivalis (Pg) is an oral pathogen with the ability to induce oral dysbiosis and periodontal disease. Nevertheless, the mechanisms by which mucosal responses to the oral microbiota in the presence of specific pathogens such as Pg could abrogate the host-microbe symbiotic relationship leading to periodontitis remain unclear. Herein, we identified the Notch-1/PLA2 -IIA axis as a new molecular pathway through which Pg could be specifically modulating oral epithelial antimicrobial and inflammatory responses...
March 7, 2018: Mucosal Immunology
Hilde Cheroutre
No abstract text is available yet for this article.
March 2018: Mucosal Immunology
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...
March 2018: Mucosal Immunology
K A Kuhn, H M Schulz, E H Regner, E L Severs, J D Hendrickson, G Mehta, A K Whitney, D Ir, N Ohri, C E Robertson, D N Frank, E L Campbell, S P Colgan
Interactions between the microbiota and distal gut are important for the maintenance of a healthy intestinal barrier; dysbiosis of intestinal microbial communities has emerged as a likely contributor to diseases that arise at the level of the mucosa. Intraepithelial lymphocytes (IELs) are positioned within the epithelial barrier, and in the small intestine they function to maintain epithelial homeostasis. We hypothesized that colon IELs promote epithelial barrier function through the expression of cytokines in response to interactions with commensal bacteria...
March 2018: Mucosal Immunology
L Shang, A J Smith, C S Reilly, L Duan, K E Perkey, S Wietgrefe, M Zupancic, P J Southern, R P Johnson, J V Carlis, A T Haase
Cervicovaginal epithelium plays a critical role in determining the outcome of virus transmission in the female reproductive tract (FRT) by initiating or suppressing transmission-facilitating mucosal immune responses in naïve and SIVmac239Δnef-vaccinated animals, respectively. In this study, we examined the very early responses of cervical epithelium within 24 h after vaginal exposure to SIV in naive and SIVmac239Δnef-vaccinated rhesus macaques. Using both ex vivo and in vivo experimental systems, we found that vaginal exposure to SIV rapidly induces a broad spectrum of pro-inflammatory responses in the epithelium associated with a reciprocal regulation of NF-kB and glucocorticoid receptor (GR) signaling pathways...
March 2018: Mucosal Immunology
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