Abstract：
:Intestinal epithelial Na+/H+ exchange facilitated by the apical NHE3 (Slc9a3) is a highly regulated process inhibited by intestinal pathogens and in inflammatory bowel diseases. NHE3-/- mice develop spontaneous, bacterially mediated colitis, and IBD-like dysbiosis. Disruption of epithelial Na+/H+ exchange in IBD may thus represent a host response contributing to the altered gut microbial ecology, and may play a pivotal role in modulating the severity of inflammation in a microbiome-dependent manner. To test whether microbiome fostered in an NHE3-deficient environment is able to drive mucosal immune responses affecting the onset or severity of colitis, we performed a series of cohousing experiments and fecal microbiome transplants into germ-free Rag-deficient or IL-10-/- mice. We determined that in the settings where the microbiome of NHE3-deficient mice was stably engrafted in the recipient host, it was able accelerate the onset and amplify severity of experimental colitis. NHE3-deficiency was characterized by the reduction in pH-sensitive butyrate-producing Firmicutes families Lachnospiraceae and Ruminococcaceae (Clostridia clusters IV and XIVa), with an expansion of inflammation-associated Bacteroidaceae. We conclude that the microbiome fostered by impaired epithelial Na+/H+ exchange enhances the onset and severity of colitis through disruption of the gut microbial ecology.
journal_name
Mucosal Immunoljournal_title
Mucosal immunologyauthors
Harrison CA,Laubitz D,Ohland CL,Midura-Kiela MT,Patil K,Besselsen DG,Jamwal DR,Jobin C,Ghishan FK,Kiela PRdoi
10.1038/s41385-018-0035-2subject
Has Abstractpub_date
2018-09-01 00:00:00pages
1329-1341issue
5eissn
1933-0219issn
1935-3456pii
10.1038/s41385-018-0035-2journal_volume
11pub_type
杂志文章abstract：:The mechanisms underlying the massive gastrointestinal tract CD4 T-cell depletion in human immunodeficiency virus (HIV) infection are not well understood nor is it clear whether similar depletion is manifest at other mucosal surfaces. Studies of T-cell and virus dynamics in different anatomical sites have begun to ill...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2007.5
更新日期：2008-01-01 00:00:00
abstract：:Rotaviruses (RV) are the leading cause of gastroenteritis in infants and children worldwide and are associated with high mortality predominately in low-income settings. The virus is classified into G and P serotypes and further into P genotypes based on differences in the surface-exposed proteins VP7 and VP4, respecti...
journal_title：Mucosal immunology
pub_type： 杂志文章,评审
doi：10.1038/mi.2014.114
更新日期：2015-01-01 00:00:00
abstract：:Mucus, with its burden of inspired particulates and pathogens, is cleared from mucosal surfaces of the airways by cilia beating within the periciliary layer (PCL). The PCL is held to be "watery" and free of mucus by thixotropic-like forces arising from beating cilia. With radii of gyration ~250 nm, however, polymeric ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2012.81
更新日期：2013-03-01 00:00:00
abstract：:Intestinal macrophages (mφ) form one of the largest populations of mφ in the body and are vital for the maintenance of gut homeostasis. They have several unique properties and are derived from local differentiation of classical Ly6Chi monocytes, but the factors driving this tissue-specific process are not understood. ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2016.142
更新日期：2017-11-01 00:00:00
abstract：:Over the past 25 years, studies led in humans have considerably improved our understanding of celiac disease, a complex disease that is generally defined as an autoimmune-like enteropathy induced by dietary gluten in genetically predisposed individuals. Recently, large efforts were also invested in the development of ...
journal_title：Mucosal immunology
pub_type： 杂志文章,评审
doi：10.1038/mi.2014.102
更新日期：2015-01-01 00:00:00
abstract：:The mammalian gut microbiota is essential for normal intestinal development, renewal, and repair. Injury to the intestinal mucosa can occur with infection, surgical trauma, and in idiopathic inflammatory bowel disease. Repair of mucosal injury, termed restitution, as well as restoration of intestinal homeostasis invol...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2013.84
更新日期：2014-05-01 00:00:00
abstract：:The development of the primitive gut in the multicellular aquatic eukaryote was driven by the insufficient absorption of nutrients from the oceanic soup. The anatomy of this evolving specialized system invited its colonization by environmental prokaryotes and resulted in the establishment of the intestinal microflora....
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2009.123
更新日期：2010-01-01 00:00:00
abstract：:Levels of reactive free radicals are elevated in the airway during asthmatic exacerbations, but their roles in the pathophysiology of asthma remain unclear. We have identified subsets of myeloid-derived suppressor-like cells as key sources of nitric oxide and superoxide in the lungs of mice with evolving experimental ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2011.16
更新日期：2011-09-01 00:00:00
abstract：:Vaccine-mediated prevention of primary infection with human immunodeficiency virus (HIV) may require the sustained production of antibody at mucosal portals of entry. Here, we describe a novel approach of repeated mucosal immunization by delivering an HIV-1 envelope glycoprotein (gp) in a gel formulated for intravagin...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2009.110
更新日期：2010-01-01 00:00:00
abstract：:There continues to be a major need for more effective inflammatory bowel disease (IBD) therapies. IL-13Rα2 is a decoy receptor that binds the cytokine IL-13 with high affinity and diminishes its STAT6-mediated effector functions. Previously, we found that IL-13Rα2 was necessary for IBD in mice deficient in the anti-in...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-019-0189-6
更新日期：2019-09-01 00:00:00
abstract：:Annual epidemics and unexpected pandemics of influenza are threats to human health. Lung immune and inflammatory responses, such as those induced by respiratory infection influenza virus, determine the outcome of pulmonary pathogenesis. Platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) has an immunoregulatory ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2017.1
更新日期：2017-11-01 00:00:00
abstract：:Children born by cesarean section (CS) have an increased risk of developing inflammatory bowel disease (IBD), possibly due to skewed microbial colonization during birth and consequently impaired bacterial stimulation of the developing immune system. The aim of this study was to investigate the association between CS a...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-019-0207-8
更新日期：2019-11-01 00:00:00
abstract：:HIV prevention mandates an understanding of the mechanisms of mucosal immunity with attention to some unique features of the epidemic and mucosal environment in the developing world. An effective vaccine will have to induce mucosal protection against a highly diverse virus, which is equipped with a number of immune ev...
journal_title：Mucosal immunology
pub_type： 杂志文章,评审
doi：10.1038/mi.2009.23
更新日期：2009-07-01 00:00:00
abstract：:Chlamydia trachomatis (Ct) is an obligate intracellular bacterial pathogen. Previously, we showed that infection of human trophoblast cells by Ct triggers the secretion of the pro-inflammatory cytokine, interleukin (IL)-1β. The aim of this study was to understand the innate immune pathways involved in trophoblast prod...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2012.63
更新日期：2013-03-01 00:00:00
abstract：:Intranasal (IN) immunization with a Plasmodium circumsporozoite (CS) protein conjugated to flagellin, a Toll-like receptor 5 agonist, was found to elicit antibody-mediated protective immunity in our previous murine studies. To better understand IN-elicited immune responses, we examined the nasopharynx-associated lymph...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2013.48
更新日期：2014-03-01 00:00:00
abstract：:Nedd4 family interacting protein 1 (Ndfip1) is an adaptor protein that regulates Itch, an E3 ubiquitin ligase that ubiquitylates JunB, thereby preventing interleukin (IL)-4 and IL-5 production. Mice lacking Ndfip1 or Itch develop T helper type 2 (T(H)2)-mediated inflammation in the skin and lungs and die prematurely. ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2010.69
更新日期：2011-05-01 00:00:00
abstract：:Mycobacterium tuberculosis (M.tb) is deposited into the alveolus where it first encounters the alveolar lining fluid (ALF) prior contacts host cells. We demonstrated that M.tb-exposure to human ALF alters its cell surface, driving better M.tb infection control by professional phagocytes. Contrary to these findings, ou...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-019-0156-2
更新日期：2019-05-01 00:00:00
abstract：:Peroxisome proliferator-activated receptor-γ (PPAR-γ) is widely expressed in macrophages and has been identified as a putative target for the development of novel therapies against inflammatory bowel disease (IBD). Computational simulations identified macrophages as key targets for therapeutic interventions against IB...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2010.75
更新日期：2011-05-01 00:00:00
abstract：:Individuals with one atopic disease are far more likely to develop a second. Approximately half of all atopic dermatitis (AD) patients subsequently develop asthma, particularly those with severe AD. This association, suggesting a role for AD as an entry point for subsequent allergic disease, is a phenomenon known as t...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2012.14
更新日期：2012-05-01 00:00:00
abstract：:The study of animal immune physiology and animal models of human disease have accelerated many aspects of translational research by allowing direct, definitive investigations. In particular, the use of mice has allowed genetic manipulation, adoptive transfer, immunization, and focused cell and tissue sampling, which w...
journal_title：Mucosal immunology
pub_type： 杂志文章,评审
doi：10.1038/mi.2010.85
更新日期：2011-03-01 00:00:00
abstract：:Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and death worldwide. Immunization with conjugated pneumococcal vaccine has lowered the colonization rate and consequently invasive diseases by inducing serotype-specific antibodies. However, many of the current pneumonia cases...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2016.41
更新日期：2017-01-01 00:00:00
abstract：:Epigallocatechin-3-gallate (EGCG), a natural and major ingredient of green tea, has been shown to have anti-inflammation and anti-HIV-1 properties. We demonstrated that the intrarectal administration of EGCG could protect rhesus macaques from repetitive, intrarectal challenges with low-dose SHIVSF162P3N. This protecti...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-018-0025-4
更新日期：2018-07-01 00:00:00
abstract：:Human type-2 CD8+ T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia-a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent ...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/s41385-018-0049-9
更新日期：2018-09-01 00:00:00
abstract：:Beryllium exposure results in beryllium hypersensitivity in a subset of exposed individuals, leading to granulomatous inflammation and fibrosis in the lung. In addition to its antigenic properties, beryllium has potent adjuvant activity that contributes to sensitization via unknown pathways. Here we show that berylliu...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2015.14
更新日期：2015-11-01 00:00:00
abstract：:The impact of topical antiretrovirals for pre-exposure prophylaxis on humoral responses following HIV infection is unknown. Using a binding antibody multiplex assay, we investigated HIV-specific IgG and IgA responses to envelope glycoproteins, p24 Gag and p66, in the genital tract (GT) and plasma following HIV acquisi...
journal_title：Mucosal immunology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1038/mi.2015.145
更新日期：2016-05-01 00:00:00
abstract：:AIDS is mainly a sexually transmitted disease, and accordingly, mucosal tissues are the primary sites of natural human immunodeficiency virus type-1 (HIV-1) transmission. Mucosal immunoglobulin A (IgA) antibody specific for HIV-1 envelope gp41 subunit is one correlate of protection in individuals who are highly sexual...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2009.89
更新日期：2009-09-01 00:00:00
abstract：:Intestinal dendritic cells (DCs) continuously migrate through lymphatics to mesenteric lymph nodes where they initiate immunity or tolerance. Recent research has focused on populations of intestinal DCs expressing CD103. Here we demonstrate, for the first time, the presence of two distinct CD103(-) DC subsets in intes...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2012.53
更新日期：2013-01-01 00:00:00
abstract：:The mucosal immune system is charged with defending the host's vast interfaces with the outside world from the enormous and diverse group of microbes that colonizes these surfaces. A key means by which the mucosal immune system protects the host from such diverse microbes is using germ-line-encoded receptors that targ...
journal_title：Mucosal immunology
pub_type： 杂志文章,评审
doi：10.1038/mi.2009.9
更新日期：2009-05-01 00:00:00
abstract：:Interleukin-17 (IL-17)-mediated immunity has emerged as a crucial host defense mechanism against Candida albicans infections in mucosal tissues and the skin. The precise mechanism by which the IL-17 pathway prevents fungal outgrowth has not been clarified. Neutrophils are critical for limiting fungal dissemination and...
journal_title：Mucosal immunology
pub_type： 杂志文章
doi：10.1038/mi.2014.57
更新日期：2015-03-01 00:00:00
abstract：:Although an enrichment of orally derived bacteria is reported in the gut microbiota of patients with several diseases, it is mostly unknown whether oral bacteria can colonize and induce intestinal inflammation. In a recent paper in Science, Atarashi et al.1 from Kenya Honda's laboratory show that a subset of orally de...
journal_title：Mucosal immunology
pub_type： 评论,杂志文章
doi：10.1038/mi.2017.116
更新日期：2018-03-01 00:00:00
