Abstract:
:Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease in cattle. The complex, multifaceted interaction of M. avium subsp. paratuberculosis with its host includes dampening the ability of infected cells to respond to stimuli that promote M. avium subsp. paratuberculosis clearance. By disrupting host defenses, M. avium subsp. paratuberculosis creates an intracellular environment that favors the establishment and maintenance of infection. Toll-like receptors (TLRs) are important sensors that initiate innate immune responses to microbial challenge and are also immunotherapeutic targets. For example, TLR9 contributes to host defense against M. avium subsp. paratuberculosis, and its agonists (CpG oligodeoxynucleotides [ODNs]) are under investigation for treatment of Johne's disease and other infections. Here we demonstrate that M. avium subsp. paratuberculosis infection changes the responsiveness of bovine monocytes to TLR9 stimulation. M. avium subsp. paratuberculosis inhibits classical TLR9-mediated responses despite a 10-fold increase in TLR9 expression and maintained uptake of CpG ODNs. Other TLR9-mediated responses, such as oxidative burst, which occur through noncanonical signaling, remain functional. Kinome analysis verifies that classic TLR9 signaling is blocked by M. avium subsp. paratuberculosis infection and that signaling instead proceeds through a Pyk2-mediated mechanism. Pyk2-mediated signaling does not hinder infection, as CpG ODNs fail to promote M. avium subsp. paratuberculosis clearance. Indeed, Pyk2 signaling appears to be an important aspect of M. avium subsp. paratuberculosis infection, as Pyk2 inhibitors significantly reduce the number of intracellular M. avium subsp. paratuberculosis bacteria. The actions of M. avium subsp. paratuberculosis on TLR9 signaling may represent a strategy to generate a host environment which is better suited for infection, revealing potential new targets for therapeutic intervention.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Arsenault RJ,Li Y,Maattanen P,Scruten E,Doig K,Potter A,Griebel P,Kusalik A,Napper Sdoi
10.1128/IAI.00785-12subject
Has Abstractpub_date
2013-01-01 00:00:00pages
226-37issue
1eissn
0019-9567issn
1098-5522pii
IAI.00785-12journal_volume
81pub_type
杂志文章abstract::Wild-type Vibrio cholerae of both El Tor and classical biotypes (strains N16961 and 395, respectively) and nonmotile mutant derivatives with and without flagellar structures were characterized in three different animal models: (i) the rabbit ileal loop, (ii) the removable intestinal tie adult rabbit diarrhea (RITARD) ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.59.8.2727-2736.1991
更新日期:1991-08-01 00:00:00
abstract::The bactericidal and opsonizing effects of normal human serum on six strains of Salmonella typhimurium LT-2 having different lipopolysaccharide (LPS) composition were demonstrated through five indices. Complement activity in the presence of antibody was important for the opsonization of all six strains and for the bac...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.49.3.647-653.1985
更新日期:1985-09-01 00:00:00
abstract::Recent work has demonstrated that the polyketide natural product Aurodox from Streptomyces goldiniensis is able to block the pathogenesis of the murine pathogen Citrobacter rodentium In this work, we aimed to gain a better understanding of the mechanism of action of the compound. We show that Aurodox downregulates the...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00595-18
更新日期:2019-01-24 00:00:00
abstract::Peritoneal exudate T lymphocytes from Listeria monocytogenes-immune mice in the presence of the homologous antigen (heat-killed L. monocytogenes) and normal macrophages showed L. monocytogenes-specific proliferative responses. Proliferation was inhibited by macrophages from L. monocytogenes- or Corynebacterium parvum-...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.38.3.907-913.1982
更新日期:1982-12-01 00:00:00
abstract::During an etiological study of Kawasaki disease (mucocutaneous lymph node syndrome [MCLS]), we found that dominant viridans streptococcal strains on tooth surfaces and in the throat of both MCLS patients and non-MCLS control children formed erythrogenic and biologically active, extracellular products. In this study, w...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.12.5252-5260.1993
更新日期:1993-12-01 00:00:00
abstract::Legionella pneumophila was mutagenized with Tn903dIIlacZ, and a collection of mutants was screened for defects in macrophage killing (Mak-). Of 4,564 independently derived mutants, 55 (1.2%) showed a reduced or complete lack in the ability to kill HL-60-derived human macrophages. Forty-nine of the Mak- mutants could b...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.12.5361-5373.1993
更新日期:1993-12-01 00:00:00
abstract::A Gram-negative, filamentous, rod-shaped bacillus which failed to grow in cell-free media was isolated in apparently pure culture from the bronchial scraping and washing of a laboratory rat suffering from chronic respiratory disease by inoculating embryonated chicken eggs via the allantoic route. None of the embryos d...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.47.2.472-479.1985
更新日期:1985-02-01 00:00:00
abstract::Phase 1 and 2 clinical trials of group B streptococcal (GBS) capsular polysaccharide (CPS)-protein conjugate vaccines in healthy adults have demonstrated their safety and improved immunogenicity compared with uncoupled CPSs. Two recent trials sought to determine (i) whether adsorption of conjugate vaccine to aluminum ...
journal_title:Infection and immunity
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/IAI.69.11.6696-6701.2001
更新日期:2001-11-01 00:00:00
abstract::Representative strains of serogroup A Neisseria meningitidis were chosen from all major meningitis epidemics worldwide since 1960 and subjected to analysis for the electrophoretic variation of 15 cytoplasmic allozymes and four outer membrane proteins. The 290 strains defined 84 unique electrophoretic types which were ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.60.12.5267-5282.1992
更新日期:1992-12-01 00:00:00
abstract::Enterohemorrhagic Escherichia coli (EHEC) is a noninvasive food-borne pathogen that colonizes the distal ileum and colon. Proteins encoded in the EHEC locus of enterocyte effacement (LEE) pathogenicity island are known to contribute to this pathogen's adherence to epithelial cells and intestinal colonization. The role...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01688-07
更新日期:2008-05-01 00:00:00
abstract::A protein factor which induces high levels of gamma interferon (IFN-gamma) in resting splenic nonadherent cells was isolated from the sera of mice with generalized inflammation caused by endotoxic shock. The factor was highly purified by ammonium sulfate precipitation followed by ion-exchange column chromatography on ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.61.1.64-70.1993
更新日期:1993-01-01 00:00:00
abstract::Ers has been qualified as the PrfA-like transcriptional regulator of Enterococcus faecalis. In a previous study we reported that Ers is important for the survival within macrophages of this opportunist pathogenic bacterium. In the present work we have used proteomic and microarray expression profiling of E. faecalis J...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00161-08
更新日期:2008-07-01 00:00:00
abstract::Our previous studies demonstrated that Mycobacterium bovis bacillus Calmette-Guérin (BCG) can directly interact with human NK cells and induce the proliferation, gamma interferon production, and cytotoxic activity of such cells without the need for accessory cells. Thus, the aim of the present study was to identify th...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00870-07
更新日期:2008-04-01 00:00:00
abstract::A genomic library of meningococcal DNA from a clinical isolate of Neisseria meningitidis was constructed in the expression vector lambda gt11. Outer membrane complex was prepared from the same strain and used to immunize rabbits to raise polyclonal anti-outer membrane complex serum. The amplified library was probed wi...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.55.11.2734-2740.1987
更新日期:1987-11-01 00:00:00
abstract::We have identified a Crp/Fnr-like transcriptional regulator of Streptococcus pyogenes that when inactivated attenuates virulence. The gene, named srv for streptococcal regulator of virulence, encodes a 240-amino-acid protein with 53% amino acid similarity to PrfA, a transcriptional activator of virulence in Listeria m...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.72.3.1799-1803.2004
更新日期:2004-03-01 00:00:00
abstract::Protein-malnourished rats had greater numbers of bacteria in their livers and spleens compared with numbers in control rats following a sublethal intraperitoneal dose of Salmonella typhimurium. However, the febrile responses of both groups of rats to infection were similar. The ability to mount a normal febrile respon...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.56.4.1000-1002.1988
更新日期:1988-04-01 00:00:00
abstract::Endogenous interleukin-12 (IL-12) mediates protection against Yersinia enterocolitica in C57BL/6 mice by triggering gamma interferon (IFN-gamma) production in NK and CD4+ T cells. Administration of exogenous IL-12 confers protection against yersiniae in Yersinia-susceptible BALB/c mice but exacerbates yersiniosis in r...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.66.5.2213-2220.1998
更新日期:1998-05-01 00:00:00
abstract::To characterize the mechanism by which interleukin 10 (IL-10) inhibits Th1 responses to intracellular pathogens, we evaluated the interaction between IL-10 and Mycobacterium tuberculosis-induced gamma interferon (IFN-gamma) production by peripheral blood mononuclear cells from persons across the spectrum of tuberculou...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.64.3.913-918.1996
更新日期:1996-03-01 00:00:00
abstract::Many pathogenic Escherichia coli produce the toxin alpha-hemolysin (Hly), and lipopolysaccharide (LPS), interleukin-1 (IL-1), and tumor necrosis factor (TNF) have all been recognized as important effector molecules during infections by gram-negative organisms. Despite the characterization of many in vitro effects of h...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:
更新日期:1998-09-01 00:00:00
abstract::Neutrophil collagenase (matrix metalloproteinase 8 [MMP-8]) is an important mediator of tissue destruction in inflammatory diseases. Studies of anaerobic periodontal infections have shown that active MMP-8 in gingival crevicular fluid is associated with the degradation of periodontal tissues in progressive periodontit...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.67.5.2319-2326.1999
更新日期:1999-05-01 00:00:00
abstract::Using fluorescent antibody techniques (FA) and light microscopy (LM) and electron microscopy (EM), this paper describes the morphological features of the ileum in the DK1 mouse orally challenged with adenovirus K87. At the peak of infection, virus is easily identified by FA in the epithelium of the villi and crypts of...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.13.2.569-580.1976
更新日期:1976-02-01 00:00:00
abstract::CD8 T cells are effective mediators of specific immunity to infection by Listeria monocytogenes, a bacterial pathogen that initially infects macrophages in the spleen and liver and subsequently spreads to hepatocytes and unidentified parenchymal cells in the spleen. To identify the in vivo target cells of L. monocytog...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.64.9.3632-3640.1996
更新日期:1996-09-01 00:00:00
abstract::Infection with Cryptosporidium parvum, a ubiquitous protozoan parasite of virtually all mammals, can cause mild to severe diarrhea in immunocompetent hosts and life-threatening diarrhea in immunocompromised hosts. Passive immunotherapy of experimentally infected animals and naturally infected humans with hyperimmune b...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.58.9.2962-2965.1990
更新日期:1990-09-01 00:00:00
abstract::Shigella flexneri 2a is an invasive enteric pathogen that may produce diarrhea when ingested by human beings and subhuman primates. We have previously shown that shigella diarrhea correlates with water and electrolyte transport abnormalities in the jejunum and colon. Dysentery alone is associated only with colonic tra...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.14.2.368-371.1976
更新日期:1976-08-01 00:00:00
abstract::The blood-stage development of malaria parasites is initiated by the invasion of merozoites into susceptible erythrocytes. Specific receptor-ligand interactions must occur for the merozoites to first attach to and then invade erythrocytes. Because the invasion process is essential for the parasite's survival and the m...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.62.12.5581-5586.1994
更新日期:1994-12-01 00:00:00
abstract::P6, a 16,600-dalton protein present in the outer membranes of both typeable and nontypeable strains, may be an important antigen in immunity to Haemophilus influenzae. The gene encoding P6 of a nontypeable strain of H. influenzae was cloned by using bacteriophage lambda gt11. Four recombinant phages were detected by s...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.56.1.128-134.1988
更新日期:1988-01-01 00:00:00
abstract::One aspect in a broad spectrum of possible mechanisms of cariostatic reactions of fluoride is its interaction with the metabolism of oral bacteria. Information on the mechanisms and kinetics of fluoride inhibition of essential enzymes of the glycolytic pathway of the relevant bacteria is lacking. In this work, the iso...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.58.4.1043-1047.1990
更新日期:1990-04-01 00:00:00
abstract::Nonimmune binding of immunoglobulin to whole bacteria was quantitated for North American isolates of Haemophilus somnus recovered from cattle with pneumonia, reproductive failure (abortion), or thromboembolic meningoencephalitis or from the vagina or prepuce of carrier cattle. Quantitative binding activity covered a w...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.57.2.639-642.1989
更新日期:1989-02-01 00:00:00
abstract::Lipoprotein I (OprI) is one of the major proteins of the outer membrane of Pseudomonas aeruginosa. OprI is a candidate for a vaccine against P. aeruginosa, because it cross-reacts antigenically in all serotype strains of the International Antigenic Typing Scheme. We recently cloned and expressed the gene coding for Op...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.58.7.2241-2244.1990
更新日期:1990-07-01 00:00:00
abstract::P.69 pertactin (P.69 Prn), an adhesion molecule from the causative agent of pertussis, Bordetella pertussis, is present in cellular and most acellular vaccines that are currently used worldwide. Although both humoral immunity and cellular immunity directed against P.69 Prn have been implicated in protective immune mec...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00769-08
更新日期:2009-02-01 00:00:00