Abstract:
:Gastroesophageal reflux (GER) frequently occurs in patients with respiratory disease and is particularly prevalent in patients with cystic fibrosis. GER is a condition in which the duodenogastric contents of the stomach leak into the esophagus, in many cases resulting in aspiration into the respiratory tract. As such, the presence of GER-derived bile acids (BAs) has been confirmed in the bronchoalveolar lavage fluid and sputum of affected patients. We have recently shown that bile causes cystic fibrosis-associated bacterial pathogens to adopt a chronic lifestyle and may constitute a major host trigger underlying respiratory infection. The current study shows that BAs elicit a specific response in humans in which they repress hypoxia-inducible factor 1α (HIF-1α) protein, an emerging master regulator in response to infection and inflammation. HIF-1α repression was shown to occur through the 26S proteasome machinery via the prolyl hydroxylase domain (PHD) pathway. Further analysis of the downstream inflammatory response showed that HIF-1α repression by BAs can significantly modulate the immune response of airway epithelial cells, correlating with a decrease in interleukin-8 (IL-8) production, while IL-6 production was strongly increased. Importantly, the effects of BAs on cytokine production can also be more dominant than the bacterium-mediated effects. However, the effect of BAs on cytokine levels cannot be fully explained by their ability to repress HIF-1α, which is not surprising, given the complexity of the immune regulatory network. The suppression of HIF-1 signaling by bile acids may have a significant influence on the progression and outcome of respiratory disease, and the molecular mechanism underpinning this response warrants further investigation.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Legendre C,Reen FJ,Woods DF,Mooij MJ,Adams C,O'Gara Fdoi
10.1128/IAI.00674-13subject
Has Abstractpub_date
2014-09-01 00:00:00pages
3531-41issue
9eissn
0019-9567issn
1098-5522pii
IAI.00674-13journal_volume
82pub_type
杂志文章abstract::Mice were infected with Chlamydia trachomatis (L2/434) and at various intervals after infection their lymphoid cells were tested directly for cytotoxic activity against Chlamydia-infected L929 cells. In a modified cell-mediated lympholysis assay, splenic, lymph node, and peritoneal exudate cells did not significantly ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.39.3.1271-1274.1983
更新日期:1983-03-01 00:00:00
abstract::In order to further characterize human host defenses against Coccidioides immitis, extracts of this fungus were tested in vitro for their ability to attract polymorphonuclear leukocytes derived from peripheral blood of uninfected subjects. Soluble substances prepared from the mycelial (saprophytic) and spherule (tissu...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.21.3.862-865.1978
更新日期:1978-09-01 00:00:00
abstract::Representative strains of oral streptococci were tested for Fc immunoglobulin G (IgG) reactivity by two different techniques, agglutination of rabbit-IgG sensitized sheep erythrocytes and uptake of human and rabbit 125I-radiolabeled IgG. None of the S. mutans serotypes a through e reacted with the Fc region of either ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.34.3.851-855.1981
更新日期:1981-12-01 00:00:00
abstract::We have previously shown that malaria parasites liberate exoantigens which, through a phospholipid component, stimulate mouse macrophages to secrete tumor necrosis factor (TNF), which are toxic to D-galactosamine-sensitized mice, and which therefore might be involved in pathology. Plasmodium yoelii exoantigens detoxif...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.60.5.1894-1901.1992
更新日期:1992-05-01 00:00:00
abstract::Understanding the regulation of human immune responses is critical for vaccine development and treating infectious diseases. We have previously shown that simultaneous engagement of the T cell receptor (TCR) and complement regulator CD46 on human CD4(+) T cells in the presence of interleukin-2 (IL-2) induces potent se...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00513-10
更新日期:2010-12-01 00:00:00
abstract::Borrelia burgdorferi undergoes differential gene expression during transmission from its tick vector to a vertebrate host. The addition of blood to a spirochete culture at 35 degrees C for 48 h had a dramatic effect on gene expression of this organism. Utilizing B. burgdorferi whole genome DNA arrays, we compared the ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.72.9.5419-5432.2004
更新日期:2004-09-01 00:00:00
abstract::Inbred mouse strains differ in their susceptibility to infection with the facultative intracellular bacterium Listeria monocytogenes, largely due to delayed or deficient innate immune responses. Previous antibody depletion studies suggested that neutrophils (polymorphonuclear leukocytes [PMN]) were particularly import...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00085-18
更新日期:2018-03-22 00:00:00
abstract::When Streptococcus pyogenes group A type 3 strain C203 (M+) and its M-protein-lacking derivative, strain C203S (M-), were treated with normal human serum in the presence of magnesium-EGTA [ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid], virulent M+ bacteria bound only 10 to 30% as much C3 and f...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.58.8.2535-2541.1990
更新日期:1990-08-01 00:00:00
abstract::Hot phenol-water extraction of smooth Brucella abortus and B. melitensis cells yielded a toxic fraction which was recovered from the phenol phase (fraction 5). Chemically, fractions 5 from both Brucella species were lipid-carbohydrate-protein-2 keto-3-deoxyoctulosonic acid complexes which were stable to heat and resis...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:
更新日期:1970-02-01 00:00:00
abstract::Infection of resistant or susceptible mice with Trichuris muris provokes mesenteric lymph node responses which are polarized towards Th2 or Th1, respectively. These responses are well documented in the literature. In contrast, little is known about the local responses occurring within the infected intestine. Through m...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.73.7.4025-4033.2005
更新日期:2005-07-01 00:00:00
abstract::We investigated the effect of the extracellular protease of Serratia marcescens on human serum constituents such as immunoglobulins, fibronectin, alpha 1-protease inhibitor, alpha 2-macroglobulin, lysozyme, and transferrin. At a very low concentration of Serratia 56-kilodalton protease (56K protease), purified human p...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.53.3.522-529.1986
更新日期:1986-09-01 00:00:00
abstract::Experiments were conducted in which rhesus monkeys were infected with mumps virus by inoculation into the parotid gland. Virus was isolated from buccal swab specimens from animals up to 6 days after inoculation. Immunofluorescence staining for mumps antigen was positive, and infectious virus was recovered from tissue ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.3.5.642-647.1971
更新日期:1971-05-01 00:00:00
abstract::Cell-mediated immunity to herpes simplex virus type 1 (HSV-1) was assessed by a lymphocytotoxicity 51-Cr-release microassay procedure, using the MA-160 human prostatic adenoma cell line chronically infected with HSV-1 and its parent cell line as control. The specific immune release mean plus or minus standard deviatio...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.12.1.76-80.1975
更新日期:1975-07-01 00:00:00
abstract::Mouse peritoneal macrophages were infected with varying numbers of Nocardia asteroides 10905, and the fate of the ingested organisms was determined by viable plate count (VPC), light microscopy (LM), immunofluorescent microscopy (IM), and electron microscopy (EM). The results obtained with these methods differed. VPC ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.9.3.576-590.1974
更新日期:1974-03-01 00:00:00
abstract::Because of the unavailability of a suitable antigen, specific in vitro lymphocyte reactivity has not been investigated in persons who have had systemic blastomycosis. Twelve persons who had recovered from blastomycosis were evaluated, and all were found to exhibit strongly positive and apparently specific in vitro cel...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.33.2.485-490.1981
更新日期:1981-08-01 00:00:00
abstract::A 10-amino-acid repeating sequence of the hemagglutinating portion of Clostridium difficile toxin A has been synthesized and used to produce antisera in rabbits. Antipeptide antibody inhibited toxin A-mediated hemagglutination and neutralized cytotoxic activity. Immunoblot analysis with the antipeptide antibody reveal...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.59.9.3151-3155.1991
更新日期:1991-09-01 00:00:00
abstract::Cells infected by Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever, display unusual intracellular morphological changes characterized by dilatation of the membranes of the endoplasmic reticulum and outer nuclear envelope. These changes are consistent with those that might be expected to occur...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.56.12.3110-3115.1988
更新日期:1988-12-01 00:00:00
abstract::We have mapped a group of virulence genes of Porphyromonas gingivalis to a single large fragment of the genome. These genes (rgpA, kgp, and hagA) all contain a consensus repeat sequence (HArep). rgpA and kgp encode cysteine proteases with Arg-X and Lys-X specificity, respectively, and hagA encodes a hemagglutinin. Gen...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.67.5.2619-2623.1999
更新日期:1999-05-01 00:00:00
abstract::A radioimmunoprecipitation method has been devised which permits the direct identification of those proteins which are both exposed on the cell surface of Haemophilus influenzae type b and accessible to antibody. Both extrinsically and intrinsically radiolabeled cells of this organism were employed as the sources of a...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.33.3.950-953.1981
更新日期:1981-09-01 00:00:00
abstract::Thirteen Habs-serotype strains could be classified into 11 groups depending on the characteristic patterns of 2-amino sugar composition; strains of serotypes 2, 5, and 7 had the same pattern, and each other serotype strain had its own distinctive pattern. In our classification, fucosamine and quinovosamine were of imp...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.15.3.692-697.1977
更新日期:1977-03-01 00:00:00
abstract::The antibacterial properties of lysozyme were investigated with oral microorganisms representing the seven serotypes (a through g) of Streptococcus mutans, Veillonella alcalescens, and the virulent (V) and avirulent (AV) strains of Actinomyces viscosus T14. Growth of bacteria in defined medium was monitored spectropho...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:
更新日期:1980-08-01 00:00:00
abstract::One of the first steps in the development of cerebral toxoplasmosis is the penetration of the blood-brain barrier, which is comprised of microvascular endothelial cells. We examined the capacity of human brain microvascular endothelial cells (HBMEC) to interact with Toxoplasma gondii. We found that stimulation of HBME...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.10.6527-6531.2001
更新日期:2001-10-01 00:00:00
abstract::The effect of bile on the expression of cholera toxin (CT) and the major subunit of the toxin-coregulated pilus (TcpA) and on motility was examined in the Vibrio cholerae O1 classical-biotype strains 0395 and 569B. Although the motility of the cells increased significantly in the presence of bile, transcription of the...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.65.3.1131-1134.1997
更新日期:1997-03-01 00:00:00
abstract::D-Amino acid oxidase (DAO) is a hydrogen peroxide-generating enzyme that uses a D-amino acid as a substrate. We hypothesized that DAO may protect against bacterial infection, because hydrogen peroxide is one of the most important molecules in the antibacterial defense systems in mammals. We show here that DAO suppress...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.06214-11
更新日期:2012-04-01 00:00:00
abstract::In Pseudomonas aeruginosa, the second messenger cyclic-di-GMP and Gac/Rsm signaling pathways are associated with the transition from acute to chronic infection. Therefore, identification of the molecular mechanisms that govern lifestyle choice in bacteria is very important. Here, we identified a novel cyclic-di-GMP mo...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00602-20
更新日期:2021-01-19 00:00:00
abstract::Cryptococcus neoformans laccase expression during murine infection was investigated in lung tissue by immunohistochemistry and immunogold electron microscopy. Laccase was detected in the fungal cell cytoplasm, cell wall, and capsule in vivo. The amount of laccase found in different sites varied as a function of the ti...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.73.5.3124-3127.2005
更新日期:2005-05-01 00:00:00
abstract::In nature, mixed Borrelia burgdorferi infections are common and possibly can be acquired by either superinfection or coinfection. Superinfection by heterologous B. burgdorferi strains has been established experimentally, although the ability of homologous B. burgdorferi clones to superinfect a host has not been studie...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01817-14
更新日期:2014-11-01 00:00:00
abstract::Helicobacter pylori vacuolating cytotoxin (VacA) is a secreted protein that induces vacuolation of epithelial cells. To study VacA structure and function, we immunized mice with purified type s1-m1 VacA from H. pylori strain 60190 and generated a panel of 10 immunoglobulin G1kappa anti-VacA monoclonal antibodies. All ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.7.4329-4336.2001
更新日期:2001-07-01 00:00:00
abstract::The she gene of Shigella flexneri 2a, which also harbors the internal enterotoxin genes set1A and set1B (F. R. Noriega, GenBank accession no. U35656, 1995) encodes a homolog of the virulence-related immunoglobulin A (IgA) protease-like family of secreted proteins, Tsh, EspC, SepA, and Hap, from an avian pathogenic Esc...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.65.11.4606-4614.1997
更新日期:1997-11-01 00:00:00
abstract::The fucose-mannose ligand (FML) complex of Leishmania donovani is a promising vaccine candidate against murine and canine visceral leishmaniasis, and its main component is a 36-kDa nucleoside hydrolase (NH36). In this study, we tested the immune response and protection induced by the purified FML, the recombinant NH36...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.73.2.812-819.2005
更新日期:2005-02-01 00:00:00