scholarly journals Adherent Invasive Escherichia coli Strains from Patients with Crohn's Disease Survive and Replicate within Macrophages without Inducing Host Cell Death

2001 ◽  
Vol 69 (9) ◽  
pp. 5529-5537 ◽  
Author(s):  
Anne-Lise Glasser ◽  
Jerome Boudeau ◽  
Nicolas Barnich ◽  
Marie-Helene Perruchot ◽  
Jean-Frederic Colombel ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Annexin V ◽  
Human Monocyte ◽  
Peritoneal Macrophages ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Infected Cells

ABSTRACT Escherichia coli strains recovered from Crohn's disease (CD) lesions are able to adhere to and invade cultured intestinal epithelial cells. We analyzed the behavior within macrophages of adherent invasive E. coli (AIEC) strains isolated from patients with CD. All the 15 AIEC strains tested were able to replicate extensively within J774-A1 cells: the numbers of intracellular bacteria increased 2.2- to 74.2-fold at 48 h over that at 1 h postinfection. By use of murine peritoneal macrophages and human monocyte-derived-macrophages, the reference AIEC strain LF82 was confirmed to be able to survive intracellularly. Transmission electron micrographs of AIEC LF82-infected macrophages showed that at 24 h postinfection, infected cells harbored large vacuoles containing numerous bacteria, as a result of the fusion of several vacuoles occurring after 8 h postinfection. No lactate dehydrogenase (LDH) release, no sign of DNA fragmentation or degradation, and no binding to fluorescein isothlocyanate-labeled annexin V were observed with LF82-infected J774-A1 cells, even after 24 h postinfection. LF82-infected J774-A1 cells secreted 2.7-fold more tumor necrosis factor alpha (TNF-α) than cells stimulated with 1 μg of lipopolysaccharide (LPS)/ml. No release of interleukin-1β was observed with LPS-prestimulated J774-A1 cells infected with AIEC LF82. These findings showed that (i) AIEC strains are able to survive and to replicate within macrophages, (ii) AIEC LF82 replication does not induce any cell death of the infected cells, and (iii) LF82-infected J774-A1 cells release high levels of TNF-α. These properties could be related to some features of CD and particularly to granuloma formation, one of the hallmarks of CD lesions.

scholarly journals Replication of Colonic Crohn's Disease Mucosal Escherichia coli Isolates within Macrophages and Their Susceptibility to Antibiotics

2007 ◽  
Vol 52 (2) ◽  
pp. 427-434 ◽  
Author(s):  
Sreedhar Subramanian ◽  
Carol L. Roberts ◽  
C. Anthony Hart ◽  
Helen M. Martin ◽  
Steve W. Edwards ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Colonic Mucosa ◽  
Human Monocyte ◽  
Fold Increase ◽  
Serum Concentrations ◽  
Similar Extent ◽  
E Coli ◽  
K 12

ABSTRACT There is increasing evidence that Escherichia coli organisms are important in Crohn's disease (CD) pathogenesis. In CD tissue they are found within macrophages, and the adherent-invasive CD ileal E. coli isolate LF82 can replicate inside macrophage phagolysosomes. This study investigates replication and antibiotic susceptibility of CD colonic E. coli isolates inside macrophages. Replication of CD colonic E. coli within J774-A1 murine macrophages and human monocyte-derived macrophages (HMDM) was assessed by culture and lysis after gentamicin killing of noninternalized bacteria and verified by electron microscopy (EM). All seven CD colonic isolates tested replicated within J774-A1 macrophages by 3 h (6.36-fold ± 0.7-fold increase; n = 7 isolates) to a similar extent to CD ileal E. coli LF82 (6.8-fold ± 0.8-fold) but significantly more than control patient isolates (5.2-fold ± 0.25-fold; n = 6; P = 0.006) and E. coli K-12 (1.0-fold ± 0.1-fold; P < 0.0001). Replication of CD E. coli HM605 within HMDM (3.9-fold ± 0.7-fold) exceeded that for K-12 (1.4-fold ± 0.2-fold; P = 0.03). EM showed replicating E. coli within macrophage vacuoles. Killing of HM605 within J774-A1 macrophages following a 3-h incubation with antibiotics at published peak serum concentrations (C max) was as follows: for ciprofloxacin, 99.5% ± 0.2%; rifampin, 85.1% ± 6.6%; tetracycline, 62.8% ± 6.1%; clarithromycin, 62.1% ± 5.6% (all P < 0.0001); sulfamethoxazole, 61.3% ± 7.0% (P = 0.0007); trimethoprim, 56.3% ± 3.4% (P < 0.0001); and azithromycin, 41.0% ± 10.5% (P = 0.03). Ampicillin was not effective against intracellular E. coli. Triple antibiotic combinations were assessed at 10% C max, with ciprofloxacin, tetracycline, and trimethoprim causing 97% ± 0.0% killing versus 86% ± 2.0% for ciprofloxacin alone. Colonic mucosa-associated E. coli, particularly CD isolates, replicate within macrophages. Clinical trials are indicated to assess the efficacy of a combination antibiotic therapy targeting intramacrophage E. coli.

scholarly journals Transcribed ultraconserved region (T-UCR) uc.261 expression is closely correlated with disease activity and intestinal permeability in Crohn’s disease

2019 ◽  
Vol 12 ◽  
pp. 175628481988073
Author(s):  
Xiao-Xian Qian ◽  
Chen-Wen Cai ◽  
Han-Yang Li ◽  
Li-Jie Lai ◽  
Dong-Juan Song ◽  
...  
Keyword(s):  
Body Weight ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Intestinal Permeability ◽  
Activity Index ◽  
Trinitrobenzene Sulfonic Acid ◽  
T84 Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Objectives: Transcribed ultraconserved region (T-UCR) uc.261 is reported to participate in intestinal mucosa barrier damage in Crohn’s disease (CD). The aim of this study was to determine the association with disease activity and intestinal permeability. Methods: Uc.261 level in colon mucosa and Harvey-Bradshaw Index (HBI) were evaluated in 20 active CD patients. Uc.261 expression and transepithelial electrical resistance (TEER) were determined in Caco2 and T84 cells treated with tumor necrosis factor alpha (TNF-α), respectively. Body weight, disease activity index (DAI), colon length, histological index (HI), intestinal permeability to FITC-dextran, uc.261, and tight junction proteins (TJPs) levels were evaluated in BALB/C mice treated with saline enema, trinitrobenzene sulfonic acid (TNBS)/ethanol enema, and anti-TNF-α monoclonal antibody injection, respectively. Results: Uc.261 expression was overexpressed in CD patients, TNF-α treated cells, and colitis mice. Uc.261 expression was positively correlated with HBI ( r = 0.582, p = 0.007) in CD patients, and positively correlated with TNF-α concentration and negatively correlated TEER in Caco2 and T84 cells (all p < 0.05). Furthermore, uc.261 was positively correlated with DAI ( r = 0.824, p = 0.008), HI ( r = 0.672, p = 0.021), and intestinal permeability ( r = 0.636, p = 0.012), while negatively correlated with body weight ( r = –0.574, p = 0.035), colon length ( r = –0.866, p = 0.017), and TJP expression (all p < 0.05) in colitis mice. Conclusions: Uc.261 expression was closely correlated with disease activity and intestinal permeability in CD. Anti-TNF-α treatment may play its role through suppressing uc.261 expression in colitis mice.

scholarly journals HEPATITIS AND PNEUMONITIS DURIN ADALIMUMAB THERAPY IN CROHN’ DISEASE: mind the histoplasmosis!

2014 ◽  
Vol 51 (1) ◽  
pp. 73-76 ◽  
Author(s):  
Bruno do Valle PINHEIRO ◽  
Áureo de Almeida DELGADO ◽  
Julio Maria Fonseca CHEBLI
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Acute Hepatitis ◽  
Histoplasma Capsulatum ◽  
Febrile Illness ◽  
Needle Aspiration ◽  
Necrosis Factor Alpha ◽  
First Case ◽  
Tnf Α ◽  
Adalimumab Therapy

Context Tumor necrosis factor-alpha (TNF-α) inhibitor therapy plays a pivotal role in the management of moderate to severe inflammatory bowel disease. Because of the role of TNF-α in the host defenses, anti-TNF therapy has been associated with an increase the risks of granulomatous infections. Objective To report the first case of adalimumab-associated invasive histoplasmosis presenting as an acute hepatitis-like syndrome and febrile pneumonitis in a patient with Crohn’s disease. Method Case report of a patient with progressive histoplasmosis confirmed by percutaneous fine needle aspiration biopsy lung and urine Histoplasma antigen. Results We present the case of a young man with CD who developed pneumonia and acute hepatitis-like features caused by Histoplasma capsulatum infection during adalimumab therapy. To the best of our knowledge, this acute hepatitis-like manifestation has never been reported as a presentation of the histoplasmosis in patients with Crohn’s disease. Conclusions This case underscores the potential risk for serious infection that may arise in this setting and should alert clinicians to the need to consider the histoplasmosis diagnosis in patients presenting with acute hepatitis-like syndrome associated with prolonged febrile illness or pneumonitis during therapy with anti-TNF-α antibodies.

scholarly journals CD44 Deficiency Is Associated with Enhanced Escherichia coli-Induced Proinflammatory Cytokine and Chemokine Release by Peritoneal Macrophages

2009 ◽  
Vol 78 (1) ◽  
pp. 115-124 ◽  
Author(s):  
Gerritje J. W. van der Windt ◽  
Cornelis van ′t Veer ◽  
Sandrine Florquin ◽  
Tom van der Poll
Keyword(s):  
Escherichia Coli ◽  
Ex Vivo ◽  
Peritoneal Macrophages ◽  
Cellular Adhesion ◽  
Autologous Serum ◽  
Blood Leukocytes ◽  
Necrosis Factor Alpha ◽  
Altered Expression ◽  
E Coli ◽  
Tnf Α

ABSTRACT CD44 is involved in several immune responses, such as cellular adhesion, migration, proliferation, and activation. Peritonitis is an important cause of sepsis, and Escherichia coli is one of the major pathogens involved therein. We sought to determine the role of CD44 in the host response to E. coli-induced abdominal sepsis and to assess the function of CD44 in the activation of primary peritoneal macrophages by E. coli or lipopolysaccharide (LPS) purified from this bacterium by using wild-type (WT) and CD44 knockout (KO) mice. CD44 KO mice already demonstrated enhanced CXC chemokine levels in peritoneal lavage fluid at 6 h after infection, whereas tumor necrosis factor alpha (TNF-α) and interleukin-6 levels were elevated at 20 h postinfection. In line with this, CD44 KO mouse peritoneal macrophages released more TNF-α and macrophage inflammatory protein 2 (MIP-2) than did WT cells upon stimulation with E. coli or LPS in the presence of autologous serum. In contrast, plasma TNF-α levels were lower in CD44 KO mice and CD44 KO blood leukocytes secreted similar amounts of TNF-α and MIP-2 upon ex vivo incubation with E. coli or LPS. The proinflammatory phenotype of CD44 KO macrophages was not associated with an altered expression of inhibitors of Toll-like receptor signaling, whereas it could be partially reversed by addition of WT serum. CD44 deficiency did not impact on leukocyte recruitment into the peritoneal cavity or organ failure. These data suggest that CD44 differentially influences cytokine and chemokine release by different leukocyte subsets.

scholarly journals Canarypox Virus-Induced Maturation of Dendritic Cells Is Mediated by Apoptotic Cell Death and Tumor Necrosis Factor Alpha Secretion

2000 ◽  
Vol 74 (23) ◽  
pp. 11329-11338 ◽  
Author(s):  
Ralf Ignatius ◽  
Mary Marovich ◽  
Erin Mehlhop ◽  
Loreley Villamide ◽  
Karsten Mahnke ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Necrosis ◽  
Apoptotic Cell ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Infected Cells ◽  
Factor Alpha ◽  
Canarypox Virus ◽  
Necrosis Factor ◽  
Dc Maturation

ABSTRACT Recombinant avipox viruses are being widely evaluated as vaccines. To address how these viruses, which replicate poorly in mammalian cells, might be immunogenic, we studied how canarypox virus (ALVAC) interacts with primate antigen-presenting dendritic cells (DCs). When human and rhesus macaque monocyte-derived DCs were exposed to recombinant ALVAC, immature DCs were most susceptible to infection. However, many of the infected cells underwent apoptotic cell death, and dying infected cells were engulfed by uninfected DCs. Furthermore, a subset of DCs matured in the ALVAC-exposed DC cultures. DC maturation coincided with tumor necrosis factor alpha (TNF-α) secretion and was significantly blocked in the presence of anti-TNF-α antibodies. Interestingly, inhibition of apoptosis with a caspase 3 inhibitor also reduced some of the maturation induced by exposure to ALVAC. This indicates that both TNF-α and the presence of primarily apoptotic cells contributed to DC maturation. Therefore, infection of immature primate DCs with ALVAC results in apoptotic death of infected cells, which can be internalized by noninfected DCs driving DC maturation in the presence of the TNF-α secreted concomitantly by exposed cells. This suggests an important mechanism that may influence the immunogenicity of avipox virus vectors.

scholarly journals Antitumor Necrosis Factor-Alpha (TNF-α) Infliximab-Induced Pleural Effusion and Pericarditis in Crohn’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
Ashley Fonseca ◽  
Julee Sunny ◽  
Lina M. Felipez
Keyword(s):  
Crohn’S Disease ◽  
Chest Pain ◽  
Pleural Effusion ◽  
Crohn's Disease ◽  
Pleural Effusions ◽  
Drug Induced ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Crohn’s disease (CD) is a chronic inflammatory disease that can be associated with intestinal and extraintestinal manifestations. Some patients are treated with infliximab, an antitumor necrosis factor-alpha (TNF-α) agent, to help them achieve and maintain clinical and biochemical remission. However, some patients with CD can present severe adverse effects such as drug-induced lupus and rarely present with pleural space and pericardium involvement. We report a case of an 18-year-old Hispanic male with CD who acquired anti-TNF-α-induced lupus after infliximab therapy presenting with pleural effusion and pericarditis. The patient presented with a 2-week history of pleuritic chest pain. Initial laboratory workup was remarkable for leukocytosis and increased inflammatory markers. Imaging and cardiovascular studies were consistent with pericarditis and pleural effusions. Serositis was initially thought to be reactive secondary to the current Mycoplasma pneumoniae infection. He was treated with colchicine 0.6 mg PO TID for six weeks and azithromycin 500 mg PO for seven days. Pain improved after discharge but resurfaced on the day of infliximab infusion. Imaging and cardiovascular studies demonstrated the persistence of pleural effusions and pericarditis. Ultrasound-guided thoracentesis was consistent with exudative pleural effusions. Rheumatological workup was remarkable for increased antihistone antibodies, consistent with drug-induced lupus. Infliximab-induced pericarditis and pleural effusions are rarely reported in the literature. It is thought that infliximab may have a proinflammatory activity or have a delayed type III hypersensitivity reaction. The first line of therapy of anti-TNF-α-induced lupus is the withdrawal of the offending drug. Our patient is unique as few cases of anti-TNF-α-induced pleural effusion and pericarditis in CD are reported. After discontinuing the offending drug, ustekinumab was started, and maintaining a steroid and colchicine regimen, the patient’s chest pain improved. Antihistone antibodies have returned to normal one month after starting ustekinumab.

scholarly journals Biology of Inflammation in Crohn's Disease: Mechanisms of Action of Anti-TNF-αAlpha Therapy

2000 ◽  
Vol 14 (suppl c) ◽  
pp. 13C-16C ◽  
Author(s):  
Stephan R Targan
Keyword(s):  
Monoclonal Antibody ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
The Body ◽  
Primary Role ◽  
T Helper 1 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
In Vitro Investigation

Several recent trials of intravenously administered antitumour necrosis factor-alpha (TNF-α) monoclonal antibody have shown dramatic responses among patients with Crohn’s disease. These results indicate a primary role for TNF-αin the mediation of altered mucosal immune function in this disease. Clinical responses in patients treated with a single infusion of anti-TNF-αpersisted for as long as one year. The prolonged period of clinical benefit shows that the effect of short term TNF-αelimination remains long after the monoclonal antibody has cleared the body. Corresponding in vitro investigation has shown that T helper 1 (Th1) -mediated cytokine production of interferon-gamma is downregulated in the involved mucosa to a level consistent with that seen in uninflamed mucosa. These results suggest that TNF-α-specific augmentation of mucosal Th1 function is the process that is altered by removal of TNF-αand that produces such persistent responses. Understanding how TNF-αmodulates mucosal Th1 function may lead to the definition of a key feature of Crohn’s disease pathogenesis.

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