The S. Typhimurium Effector SopE Induces Caspase-1 Activation in Stromal Cells to Initiate Gut Inflammation

Müller, Andreas J.; Hoffmann, Claudia; Galle, Marlies; Broeke, A Van Den; Heikenwälder, M; Falter, Laura; Misselwitz, Benjamin; Kremer, Marcus; Beyaert, Rudi; Hardt, Wolf‐Dietrich

doi:10.1016/j.chom.2009.07.007

Cited by 137 publications

(185 citation statements)

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“…7,15,30,31 It has also been recently reported that S. Typhimurium can induce caspase 1-mediated death of stromal cells. 18 Considering that the proinflammatory cytokines IL-1 and IL-18 are substrates of caspase 1, being cleaved and activated during the caspase 1-mediated macrophage cell death, this mechanism of Salmonella-induced macrophage death is thought to be a significant proinflammatory mechanism during S. Typhimurium infection, and therefore it has been named pyroptosis, which can be triggered not only by S. Typhimurium but also by several infectious or noninfectious pathological stimuli. 2 The role of caspase 1 during S. Typhimurium infection has been studied in the mouse.…”

Section: Discussionmentioning

confidence: 99%

Enteric Pathology and Salmonella-Induced Cell Death in Healthy and SIV-Infected Rhesus Macaques

et al. 2010

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The goal of this study was to morphologically characterize a ligated ileal loop model of Salmonella enterica serotype Typhimurium infection in rhesus macaques (Macaca mulatta) and to verify the occurrence of Salmonella-induced cell death in vivo. Eight adult healthy male rhesus macaques were used for ligated ileal loop surgery. Four macaques had been intravenously inoculated with simian immunodeficiency virus (SIV) mac251. Ileal ligated loops were inoculated with wild-type (WT) S. Typhimurium strain IR715 (ATCC14028 nal r ), an isogenic noninvasive mutant strain (ATCC14028 nal r DsipADsopABDE2), or sterile Luria Bertani broth. Loops were surgically removed at 2, 5, and 8 hours post-inoculation (hpi). Intestinal samples were processed for histopathology, immunohistochemistry for detecting Salmonella, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and transmission electron microscopy. Combined histopathology scores were similar between SIV-infected and control macaques. As expected, the invasion-deficient mutant was less pathogenic than WT S. Typhimurium. Neutrophil infiltrate in the intestinal mucosa correlated with bacterial loads (r ¼ 0.7148; P < .0001) and fluid accumulation (r ¼ 0.6019; P < .0001) in the lumen of the intestinal loops. Immunolabeled WT S. Typhimurium was observed in the epithelium and lamina propria at the tip of the villi at 2 hpi, progressing toward deeper lamina propria at 5-8 hpi. Most TUNEL-positive cells localized to the lamina propria, and some had morphological features of macrophages. Ultrastructurally, bacteria were observed intracellularly in the lamina propria as well as within apoptotic bodies. This study provides morphological evidence of Salmonellainduced cell death in vivo in a relevant nonhuman primate model.

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Section: Discussionmentioning

confidence: 99%

Enteric Pathology and Salmonella-Induced Cell Death in Healthy and SIV-Infected Rhesus Macaques

et al. 2010

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“…SopE activates several innate immune signaling pathways [124] and is of major importance for eliciting intestinal inflammation [229] through activation of caspase-1 in enterocytes [280]. Caspase-1 activation results in cleavage and secretion of IL-1β and IL-18, which are important for the inflammatory response.…”

Section: Sope and Sope2mentioning

confidence: 99%

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

Ramos‐Morales

2012

ISRN Cell Biology

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Type III secretion systems are molecular machines used by many Gram-negative bacterial pathogens to inject proteins, known as effectors, directly into eukaryotic host cells. These proteins manipulate host signal transduction pathways and cellular processes to the pathogen's advantage. Salmonella enterica possesses two virulence-related type III secretion systems that deliver more than forty effectors. This paper reviews our current knowledge about the functions, biochemical activities, host targets, and impact on host cells of these effectors. First, the concerted action of effectors at the cellular level in relevant aspects of the interaction between Salmonella and its hosts is analyzed. Then, particular issues that will drive research in the field in the near future are discussed. Finally, detailed information about each individual effector is provided.

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“…5 In patients with NTS, diarrhea is a result of bacterial type III effector protein's activation of proinflammatory caspase-1 in the intestinal mucosa and to the subsequent secretion of the cytokine IL-1β. 28 Because diarrhea is a defense mechanism that depends on a healthy immune system, NTS bacteremia not associated with diarrhea quite possibly warrants an immunodeficiency evaluation. 27,29 HTN, and AF AF = atrial fibrillation; CAD = coronary artery disease; CHF = congestive heart failure; DM = diabetes mellitus; ESRD = endstage renal disease; F = female; HD = hemodialysis; HIV = human immunodeficiency virus; HTN = hypertension; ITP = idiopathic thrombocytopenic purpura; M = male; MI = myocardial infarction; PC = pericardiocentesis; RA = rheumatoid arthritis; RF = renal failure; SLE = systemic lupus erythematosus; TC = thoracentesis; WBC = white blood cell Recurrent Salmonella septicemia is an acquired immunodeficiency syndrome-defining illness.…”

Section: Immunodeficiencymentioning

confidence: 99%

Nontyphoidal Cardiac Salmonellosis: Two Case Reports and a Review of the Literature

Ortiz

Siegal

Kramer

et al. 2014

Texas Heart Institute Journal

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1 Salmonella enteritidis is the most common serotype, presumably as a consequence of frequent chicken and egg contamination.1,2 Most cases of salmonellosis are limited to gastroenteritis, but bacteremia occurs in 3% to 8% of infections; cardiovascular infections, including pericarditis and endocarditis, develop in 1% to 5% of patients.3,4 The pathogenesis of cardiac salmonellosis is related to the quantity of bacteria ingested, the characteristic ability of Salmonella to adhere to damaged endothelium, the strength of the host's immune response, and the host's previous exposure. The sequelae of Salmonella endocarditis, including valve perforation, valve ring abscess, atrioventricular wall perforation, and cusp rupture, result in an estimated mortality rate of up to 75%. 5,6 Identifying patients at risk of cardiovascular salmonellosis is important for early diagnosis and treatment. Case Reports Patient 1A 73-year-old woman presented after 3 days of progressive nausea, diarrhea, fevers, and weakness. Her medical history was significant for asthma, hypertension, and replacements (4 years earlier) of both mechanical mitral and bioprosthetic aortic valves.The patient's initial temperature was 101 °F, her blood pressure was 59/31 mmHg, and her heart rate was 74 beats/min. An electrocardiogram (ECG) showed sinus rhythm. Her white blood cell count was 8,200 K/µL; blood urea-nitrogen level, 42 mg/dL; creatinine level, 2.04 mg/dL; and initial venous lactate level, 1.3 mmol/L. Urinalysis showed 26 to 100 white cells per high-power field, and a chest radiograph showed bilateral pulmonary infiltrates. She was stabilized, started on intravascular levofloxacin (0.75 mg/kg/d), and admitted to the intensive care unit, where she developed rigors and respiratory distress that necessitated endotracheal intubation and mechanical ventilation. A repeat ECG showed a new pattern of left bundle-branch block. An echocardiogram showed heavy mitral annular calcification, which produced a dense artifact around the sewing ring that suggested endocarditis.On the 2nd day of hospitalization, blood-culture results were positive for gramnegative rods. Transesophageal echocardiography revealed an aortic valve abscess and a 1.1 × 0.5-cm vegetation (with a central cavitation) on her mechanical mitral valve (Fig. 1). The presumed source of the endocarditis was the urinary tract infection,

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The S. Typhimurium Effector SopE Induces Caspase-1 Activation in Stromal Cells to Initiate Gut Inflammation

Cited by 137 publications

References 51 publications

Enteric Pathology and Salmonella-Induced Cell Death in Healthy and SIV-Infected Rhesus Macaques

Enteric Pathology and Salmonella-Induced Cell Death in Healthy and SIV-Infected Rhesus Macaques

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

Nontyphoidal Cardiac Salmonellosis: Two Case Reports and a Review of the Literature

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