scholarly journals Interleukin-8 Controls Bacterial Transepithelial Translocation at the Cost of Epithelial Destruction in Experimental Shigellosis

1999 ◽  
Vol 67 (3) ◽  
pp. 1471-1480 ◽  
Author(s):  
P. J. Sansonetti ◽  
J. Arondel ◽  
M. Huerre ◽  
A. Harada ◽  
K. Matsushima
Keyword(s):  
Lamina Propria ◽  
Shigella Flexneri ◽  
Rabbit Model ◽  
Interleukin 8 ◽  
Bacterial Invasion ◽  
Cellular Interactions ◽  
Entry Site ◽  
Destructive Inflammation ◽  
Epithelial Lesions ◽  
The Cost

ABSTRACT In shigellosis, the network of cellular interactions mediated by a balance of pro- and anti-inflammatory cytokines or chemokines is clearly tipped toward acute destructive inflammation of intestinal tissues by the bacterial invader. This work has addressed the role played by interleukin-8 (IL-8) in a rabbit model of intestinal invasion by Shigella flexneri. IL-8, which is largely produced by the epithelial cells themselves, appears to be a major mediator of the recruitment of polymorphonuclear leukocytes (PMNs) to the subepithelial area and transmigration of these cells through the epithelial lining. Neutralization of IL-8 function by monoclonal antibody WS-4 caused a decrease in the amount of PMNs streaming through the lamina propria and the epithelium, thus significantly attenuating the severity of epithelial lesions in areas of bacterial invasion. These findings are in agreement with our previous work (31). In contrast to the PMNs, the bacteria displayed increased transepithelial translocation, as well as overgrowth in the lamina propria and increased passage into the mesenteric blood. By mediating eradication of bacteria at their epithelial entry site, although at the cost of severe epithelial destruction, IL-8 therefore appears to be a key chemokine in the control of bacterial translocation.

scholarly journals Evaluation of Putative Type II Toxin-Antitoxin Systems and Lon Protease Expression in Shigella flexneri Following Infection of Caco-2 Cells

2020 ◽  
Vol 15 (3) ◽  
Author(s):  
Erfan Kheradmand ◽  
Shabnam Razavi ◽  
Malihe Talebi ◽  
Mahmood Jamshidian
Keyword(s):  
Cell Line ◽  
Post Infection ◽  
Shigella Flexneri ◽  
Fold Increase ◽  
Expression Level ◽  
Bacterial Invasion ◽  
P Value ◽  
Lon Protease ◽  
Expression Levels ◽  
Pcr Method

: Shigella flexneri causes bacillary dysentery in developing countries. Due to recent reports regarding antimicrobial resistance in human S. flexneri, finding alternative therapeutics is of vital importance. Toxin-antitoxin (TA) systems have recently been introduced as antimicrobial targets owing to their involvement in bacterial survival in stress conditions and “persister” cell formation. In this study, the presence of four TA loci were studied in S. flexneri ATCC 12022. The presence of genes coding for the identified TA loci and Lon protease were confirmed by the PCR method using specific primers. Caco-2 cell lines were then infected with this standard strain, and 8 and 24 h post-infection, expression levels of genes coding for the studied TA loci, and Lon protease were evaluated using a real-time PCR method. Expression of mazF, GNAT (Gcn5-related N-acetyltransferase), yeeU, pfam13975, and Lon genes showed 5.4, 9.8, 2.3, 2.7, and 13.8-fold increase, respectively, 8 h after bacterial invasion of the Caco-2 cell line. In addition, the expression of the aforementioned genes showed 4.8, 10.8, 2.3, 3.7, and 16.8-fold increase after 24 h. The GNAT and lon genes showed significantly higher expression levels compared to the control (P value < 0.05). However, the increase in the expression level of yeeU was the same at 8 h and 24 h post-infection. In addition, mazF expression level showed a slight decrease at 24 h compared to 8h post-infection. Genes coding for GNAT and Lon protease showed a significantly higher expression after invading the Caco-2 cell line. Therefore, targeting GNAT or Lon protease can be taken into consideration for finding novel antimicrobial drug strategies. The exact functions and mechanisms of TA systems in S. flexneri isolates are suggested to be experimentally determined.

scholarly journals Hierarchies of Host Factor Dynamics at the Entry Site of Shigella flexneri during Host Cell Invasion

2012 ◽  
Vol 80 (7) ◽  
pp. 2548-2557 ◽  
Author(s):  
Soudeh Ehsani ◽  
José Carlos Santos ◽  
Cristina D. Rodrigues ◽  
Ricardo Henriques ◽  
Laurent Audry ◽  
...  
Keyword(s):  
Host Cell ◽  
Tyrosine Kinases ◽  
Time Course ◽  
Shigella Flexneri ◽  
Time Lapse ◽  
Small Gtpases ◽  
Host Factors ◽  
Host Cells ◽  
Entry Site ◽  
Content Type

ABSTRACTShigella flexneri, the causative agent of bacillary dysentery, induces massive cytoskeletal rearrangement, resulting in its entry into nonphagocytic epithelial cells. The bacterium-engulfing membrane ruffles are formed by polymerizing actin, a process activated through injected bacterial effectors that target host small GTPases and tyrosine kinases. Once inside the host cell,S. flexneriescapes from the endocytic vacuole within minutes to move intra- and intercellularly. We quantified the fluorescence signals from fluorescently tagged host factors that are recruited to the site of pathogen entry and vacuolar escape. Quantitative time lapse fluorescence imaging revealed simultaneous recruitment of polymerizing actin, small GTPases of the Rho family, and tyrosine kinases. In contrast, we found that actin surrounding the vacuole containing bacteria dispersed first from the disassembling membranes, whereas other host factors remained colocalized with the membrane remnants. Furthermore, we found that the disassembly of the membrane remnants took place rapidly, within minutes after bacterial release into the cytoplasm. Superresolution visualization of galectin 3 through photoactivated localization microscopy characterized these remnants as small, specular, patchy structures between 30 and 300 nm in diameter. Using our experimental setup to track the time course of infection, we identified theS. flexnerieffector IpgB1 as an accelerator of the infection pace, specifically targeting the entry step, but not vacuolar progression or escape. Together, our studies show that bacterial entry into host cells follows precise kinetics and that this time course can be targeted by the pathogen.

Early Colonic Lesions in Experimental Shigella Infection in Rhesus Monkeys: Revisited

1982 ◽  
Vol 19 (7_suppl) ◽  
pp. 1-8 ◽  
Author(s):  
A. Takeuchi
Keyword(s):  
Epithelial Cells ◽  
Lamina Propria ◽  
Macaca Mulatta ◽  
Rhesus Monkeys ◽  
Goblet Cells ◽  
Intestinal Lumen ◽  
Surface Epithelium ◽  
Bacterial Invasion ◽  
Acute Colitis ◽  
Columnar Cells

Rhesus monkeys (Macaca mulatta), given 3 × 108 to 5 × 1010Shigella flexneri 2a orally, developed signs of acute shigellosis within 24 hours. A diffuse acute colitis was well established at 48 hours. The inflammatory reaction was confined to the mucosa. The submucosa showed only edema. The shigellae were found predominantly in the columnar cells of the surface epithelium, less frequently in those of the crypt, and least frequently in the lamina propria. Shigella bacilli invaded the columnar cells from the intestinal lumen. The bacilli multiplied within epithelial cells and spread laterally to adjacent epithelial cells and penetrated the lamina propria. The bacterial invasion affected epithelial cells unevenly and resulted in the disappearance of goblet cells and pyknotic shrinkage of the surface epithelial cells. Epithelial cells had abnormal and accelerated exfoliation which resulted in multifocal epithelial defects. There was a distinct correlation between the quantity of bacilli present in tissues and the intensity of the inflammatory response. The small intestines were spared.

P0890 LAMINA PROPRIA AND CIRCULATING INTERLEUKIN-8 IN NEWLY AND PREVIOUSLY DIAGNOSED PEDIATRIC IBD PATIENTS

2004 ◽  
Vol 39 (Supplement 1) ◽  
pp. S396
Author(s):  
K. A. Brown ◽  
K. P. Reddy ◽  
J. E. Markowitz ◽  
E. D. Ruchelli ◽  
R. N. Baldassano
Keyword(s):  
Lamina Propria ◽  
Interleukin 8 ◽  
Pediatric Ibd

scholarly journals Lesions Associated with Coccidiosis in Nursing Piglets

1981 ◽  
Vol 18 (1) ◽  
pp. 21-28 ◽  
Author(s):  
S. L. Eustis ◽  
D. T. Nelson
Keyword(s):  
Viral Infection ◽  
Lamina Propria ◽  
Villous Atrophy ◽  
Enteric Pathogens ◽  
Clinical Disease ◽  
Bacterial Invasion ◽  
Necrotic Enteritis

Of 45 piglets with diarrhea, 28 had coccidiosis, with no evidence of concurrent viral infection. Villous atrophy and necrotic enteritis were the characteristic lesions, and were more severe in piglets with combined viral and coccidial infections than with coccidiosis alone. Necrotic enteritis presumably was caused by bacterial invasion of the villous lamina propria at foci denuded of epithelium by coccidia, viruses or both. Consistent lesions associated with coccidia in piglets not infected by other primary enteric pathogens suggest that coccidia are the cause of significant clinical disease in nursing piglets 6 to 15 days old.

scholarly journals Models of Invasion of Enteric and Periodontal Pathogens Into Epithelial Cells: A Comparative Analysis

1997 ◽  
Vol 8 (4) ◽  
pp. 389-409 ◽  
Author(s):  
D.H. Meyer ◽  
K.P. Mintz ◽  
P.M. Fives-Taylor
Keyword(s):  
Epithelial Cells ◽  
Host Cell ◽  
Cell Function ◽  
Shigella Flexneri ◽  
Host Cells ◽  
Bacterial Invasion ◽  
Periodontal Pathogens ◽  
Chronic Infections ◽  
Enteropathogenic Bacteria ◽  
Bacteroides Gingivalis

Bacterial invasion of epithelial cells is associated with the initiation of infection by many bacteria. To carry out this action, bacteria have developed remarkable processes and mechanisms that co-opt host cell function and stimulate their own uptake and adaptation to the environment of the host cell. Two general types of invasion processes have been observed. In one type, the pathogens (e.g., Salmonella and Yersinia spp.) remain in the vacuole in which they are internalized and replicate within the vacuole. In the other type, the organism (e.g., Actinobacillus actinomycetemcomitans, Shigella flexneri, and Listeria monocytogenes) is able to escape from the vacuole, replicate in the host cell cytoplasm, and spread to adjacent host cells. The much-studied enteropathogenic bacteria usurp primarily host cell microfilaments for entry. Those organisms which can escape from the vacuole do so by means of hemolytic factors and C type phospholipases. The cell-to-cell spread of these organisms is mediated by microfilaments. The investigation of invasion by periodontopathogens is in its infancy in comparison with that of the enteric pathogens However, studies to date on two invasive periodontopathogens, A. actinomycetemcomitans and Porphyromonas (Bacteroides) gingivalis, reveal that these bacteria have developed invasion strategies and mechanisms similar to those of the enteropathogens. Entry of A. actinomycetemcomitans is mediated by microfilaments, whereas entry of P. gingivalis is mediated by both microfilaments and microtubules. A. actinomycetemcomitans, like Shigella and Listeria, can escape from the vacuole and spread to adjacent cells. However, the spread of A. actinomycetemcomitans is linked to host cell microtubules, not microfilaments. The paradigms presented establish that bacteria which cause chronic infections, such as periodontitis, and bacteria which cause acute diseases, such as dysentery, have developed similar invasion strategies.

scholarly journals IpaD of Shigella flexneri Is Independently Required for Regulation of Ipa Protein Secretion and Efficient Insertion of IpaB and IpaC into Host Membranes

2005 ◽  
Vol 73 (3) ◽  
pp. 1432-1440 ◽  
Author(s):  
Wendy L. Picking ◽  
Hiroaki Nishioka ◽  
Patricia D. Hearn ◽  
M. Aaron Baxter ◽  
Amanda T. Harrington ◽  
...  
Keyword(s):  
Protein Secretion ◽  
Shigella Flexneri ◽  
Erythrocyte Membranes ◽  
Bacterial Invasion ◽  
Cellular Invasion ◽  
Host Cytoplasm ◽  
Host Membrane ◽  
Direct Outcome ◽  
Intercellular Spread

ABSTRACT Shigella flexneri causes human dysentery after invading the cells of the colonic epithelium. The best-studied effectors of Shigella entry into colonocytes are the invasion plasmid antigens IpaC and IpaB. These proteins are exported via a type III secretion system (TTSS) to form a pore in the host membrane that may allow the translocation of other effectors into the host cytoplasm. TTSS-mediated secretion of IpaD is also required for translocation pore formation, bacterial invasion, and virulence, but the mechanistic role of this protein is unclear. IpaD is also known to be involved in controlling Ipa protein secretion, but here it is shown that this activity can be separated from its requirement for cellular invasion. Amino acids 40 to 120 of IpaD are not essential for IpaD-dependent invasion; however, deletions in this region still lead to constitutive IpaB/IpaC secretion. Meanwhile, a central deletion causes only a partial loss of control of Ipa secretion but completely eliminates IpaD's invasion function, indicating that IpaD's role in invasion is not a direct outcome of its ability to control Ipa secretion. As shigellae expressing ipaD N-terminal deletion mutations have reduced contact-mediated hemolysis activity and are less efficient at introducing IpaB and IpaC into erythrocyte membranes, it is possible that IpaD is responsible for insertion of IpaB/IpaC pores into target cell membranes. While efficient insertion of IpaB/IpaC pores is needed for optimal invasion efficiency, it may be especially important for Ipa-dependent membrane disruption and thus for efficient vacuolar escape and intercellular spread.

III. Shigellosis: from symptoms to molecular pathogenesis

2001 ◽  
Vol 280 (3) ◽  
pp. G319-G323 ◽  
Author(s):  
Philippe J. Sansonetti
Keyword(s):  
Early Stage ◽  
Shigella Flexneri ◽  
Surface Protein ◽  
Nuclear Factor Κb ◽  
Small Gtpases ◽  
Bacterial Invasion ◽  
Cell Cytoplasm ◽  
Bacterial Surface ◽  
Dependent Process ◽  
Complex Signaling

Interaction of Shigella flexneri with epithelial cells includes contact of bacteria with the cell surface and release of Ipa proteins through a specialized type III secreton. A complex signaling process involving activation of small GTPases of the Rho family and c- src causes major rearrangements of the subcortical cytoskeleton, thereby allowing bacterial entry by macropinocytosis. After entry, shigellae escape to the cell cytoplasm and initiate intracytoplasmic movement through polar nucleation and assembly of actin filaments caused by bacterial surface protein IcsA, which binds and activates neuronal Wiskoff-Aldrich syndrome protein (N-WASP), thus inducing actin nucleation in an Arp 2/3-dependent mechanism. Actin-driven motility promotes efficient colonization of the host cell cytoplasm and rapid cell-to-cell spread via protrusions that are engulfed by adjacent cells in a cadherin-dependent process. Bacterial invasion turns infected cells to strongly proinflammatory cells through sustained activation of nuclear factor-κB. A major consequence is interleukin (IL)-8 production, which attracts polymorphonuclear leukocytes (PMNs). On transmigration, PMNs disrupt the permeability of this epithelium and promote its invasion by shigellae. At the early stage of infection, M cells of the follicle-associated epithelium allow bacterial translocation. Subsequent apoptotic killing of macrophages in a caspase 1-dependent process causes the release of IL-1β and IL-18, which accounts for the initial steps of inflammation.

Atorvastatin reduces NF-κB activity and the expression of Interleukin-8, Metalloproteinase-3 and Cyclooxygenase-2 in a rabbit model of atherosclerosis

2000 ◽  
Vol 151 (1) ◽  
pp. 34
Author(s):  
M.A Hernández-Presa ◽  
J Tuñon ◽  
M Ortego ◽  
S Mas ◽  
J.L Martín-Ventura ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Cyclooxygenase 2 ◽  
Interleukin 8

scholarly journals Adipose-Derived Mesenchymal Stem Cells in the Regeneration of Vocal Folds: A Study on a Chronic Vocal Fold Scar

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Angelou Valerie ◽  
Kalodimou Vassiliki ◽  
Messini Irini ◽  
Psychalakis Nikolaos ◽  
Eleftheria Karampela ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hyaluronic Acid ◽  
Lamina Propria ◽  
Vocal Fold ◽  
Rabbit Model ◽  
Vocal Folds ◽  
Scar Tissue ◽  
Elastic Fibers ◽  
Adipose Derived Stem Cells ◽  
Vocal Fold Scar

Background. The aim of the study was to assess the histological effects of autologous infusion of adipose-derived stem cells (ADSC) on a chronic vocal fold scar in a rabbit model as compared to an untreated scar as well as in injection of hyaluronic acid.Study Design. Animal experiment.Method. We used 74 New Zealand rabbits. Sixteen of them were used as control/normal group. We created a bilateral vocal fold wound in the remaining 58 rabbits. After 18 months we separated our population into three groups. The first group served as control/scarred group. The second one was injected with hyaluronic acid in the vocal folds, and the third received an autologous adipose-derived stem cell infusion in the scarred vocal folds (ADSC group). We measured the variation of thickness of the lamina propria of the vocal folds and analyzed histopathologic changes in each group after three months.Results. The thickness of the lamina propria was significantly reduced in the group that received the ADSC injection, as compared to the normal/scarred group. The collagen deposition, the hyaluronic acid, the elastin levels, and the organization of elastic fibers tend to return to normal after the injection of ADSC.Conclusions. Autologous injection of adipose-derived stem cells on a vocal fold chronic scar enhanced the healing of the vocal folds and the reduction of the scar tissue, even when compared to other treatments.

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