scholarly journals Humoral Immunity against Capsule Polysaccharide Protects the Host from magA+Klebsiella pneumoniae-Induced Lethal Disease by Evading Toll-Like Receptor 4 Signaling

2008 ◽  
Vol 77 (2) ◽  
pp. 615-621 ◽  
Author(s):  
Ming-Fang Wu ◽  
Chih-Ya Yang ◽  
Tzu-Lung Lin ◽  
Jin-Town Wang ◽  
Feng-Ling Yang ◽  
...  

ABSTRACT Klebsiella pneumoniae magA (for mucoviscosity-associated gene A) is linked to the pathogenesis of primary pyogenic liver abscess, but the underlying mechanism by which magA increases pathogenicity is not well elucidated. In this study, we investigated the role of the capsular polysaccharides (CPS) in the pathogenesis of magA + K. pneumoniae by comparing host immunity to magA + K. pneumoniae and a ΔmagA mutant. We found that Toll-like receptor 4 recognition by magA + K. pneumoniae was hampered by the mucoviscosity of the magA + K. pneumoniae CPS. Interestingly, monoclonal antibodies (MAbs) against magA + K. pneumoniae CPS recognized all of the K1 strains tested but not the ΔmagA and non-K1 strains. Moreover, the anti-CPS MAbs protected mice from magA + K. pneumoniae-induced liver abscess formation and lethality. This indicates that the K1 epitope is a promising target for vaccine development, and anti-CPS MAbs has great potential to protect host from K1 strain-induced mortality and morbidity in diabetic and other immunocompromised patients in the future.

Author(s):  
Nenad Pandak ◽  
Asmaa S. Mahdi ◽  
Ali Al Majrafi ◽  
Mariya Molay ◽  
Stepen S. Deenadayalan ◽  
...  

Objectives: Liver abscess can develop as a complication of hepatobiliary disease or other intraabdominal infections, but more recently it is associated with primary and secondary liver malignancies and their treatment. The goal of this study was to analyze the epidemiology, etiology and clinical characteristics of pyogenic liver abscess in Oman. The intention was to obtain the information needed for the adequate liver abscess empirical treatment. Methods: This retrospective study took place in a tertiary hospital. Consecutive patients treated for the liver abscess during the five years period, from January 2013 until the end of 2017, were enrolled. Their demographic and clinical data were used to study the characteristics of pyogenic liver abscess in Oman. Results: Fifty-three patients with pyogenic liver abscess were enrolled in the study. They were predominantly male and younger than 60 years. Klebsiella pneumoniae was the most usual bacteria causing the liver abscess. Clinical presentation was unspecific and the abdominal pain and high fever were the most usual symptoms. Conclusion: The majority of pyogenic liver abscesses are caused by K. pneumoniae so the empirical treatment should be started with antibiotic directed against it. Further studies are needed to establish the local role of anaerobic bacteria in pyogenic liver abscess as well as to monitor the presence of hypervirulent K. pneumoniae in Oman. Keywords: Pyogenic liver abscess; Etiology; Epidemiology; Klebsiella pneumoniae.


Author(s):  
Hussam Mousa ◽  
Ghada Salameh Mohammed Al-Bluwi ◽  
Zainab Fathi Mohammed Al Drini ◽  
Huda Imam Gasmelseed ◽  
Jamal Aldeen Alkoteesh ◽  
...  

Abstract Background There is a dearth of information on liver abscesses in the United Arab Emirates. Herein, we describe the clinical features of liver abscesses and determine their incidence rates and clinical outcomes. Methods We retrospectively reviewed the clinical charts of adult patients with a primary diagnosis of liver abscess at a major hospital over a 7-year period. Results Amongst 45 patients, 82.2% (37/45) had a pyogenic liver abscess (PLA) and 17.8% (8/45) had amoebic liver abscesses (ALA). Overall, patients were young (median age 42 years, IQR 35–52), mostly males (77.8%, 35/45) from the Indian subcontinent (55.6%, 25/45), presented with fever (88.9%, 40/45) and abdominal pain (88.9%, 40/45), and had a solitary abscess on imaging (71.1% (32/45). Crude annual incidence rates were 35.9/100,000 hospital admissions (95% CI 26.2–48.0) and 5.9/100,000 inhabitants (95% CI 4.3–7.9). All ALA patients were from the Indian subcontinent (100%, 8/8). Klebsiella pneumoniae was the most frequent pathogen in PLA (43.2% [16/37], 95% CI 27.1–60.5%). The hospital stay was shorter in ALA (7.5 days, IQR 7–8.5) than in PLA (14 days, IQR 9–17). No deaths were recorded within 30 days of hospitalisation. Conclusions ALA was exclusively seen in migrants from the Indian subcontinent, suggesting importation. Further research to characterise K. pneumoniae isolates and assess potential risk factors is needed.


2013 ◽  
Vol 57 (5) ◽  
pp. 77S
Author(s):  
Ali Navi ◽  
Rebekah Yu ◽  
Xu Shi-Wen ◽  
Sidney Shaw ◽  
George Hamilton ◽  
...  

Zygote ◽  
2021 ◽  
pp. 1-7
Author(s):  
Júlio Panzera Gonçalves ◽  
Breno Augusto Magalhães ◽  
Paulo Henrique Almeida Campos-Junior

Abstract Toll-like receptor 4 (TLR4) is best known for its role in bacteria-produced lipopolysaccharide recognition. Regarding female reproduction, TLR4 is expressed by murine cumulus cells and participates in ovulation and in cumulus–oocyte complex (COC) expansion, maternal–fetal interaction and preterm labour. Despite these facts, the role of TLR4 in ovarian physiology is not fully understood. Therefore, the aim of the present study was to investigate the effects of TLR4 genetic ablation on mice folliculogenesis and female fertility, through analysis of reproductive crosses, ovarian responsiveness and follicular quantification in TLR4−/− (n = 94) and C57BL/6 mice [wild type (WT), n = 102]. TLR4-deficient pairs showed a reduced number of pups per litter (P = 0.037) compared with WT. TLR4−/− mice presented more primordial, primary, secondary and antral follicles (P < 0.001), however there was no difference in estrous cyclicity (P > 0.05). A lower (P = 0.006) number of COC was recovered from TLR4−/− mice oviducts after superovulation, and in heterozygous pairs, TLR4−/− females also showed a reduction in the pregnancy rate and in the number of fetuses per uterus (P = 0.007) when compared with WT. Altogether, these data suggest that TLR4 plays a role in the regulation of murine folliculogenesis and in determining ovarian endowment. TLR4 deficiency may affect ovulation and pregnancy rates, potentially decreasing fertility, therefore the potential side effects of its blockade have to be carefully investigated.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hwi Jin Ko ◽  
Dae Young Jung ◽  
Zhexi Ma ◽  
Jason K Kim

Increasing evidence implicates the role of inflammation in diabetes and complications. Macrophages are shown to infiltrate adipose tissue in obesity, and inflammatory cytokines alter glucose metabolism in peripheral organs. Male C57BL/6 mice were fed high-fat diet (HFD; 55% fat by calories) or chow diet for 6 weeks, and heart samples were taken for analysis (n = 5~7). Chronic HFD increased whole body fat mass, measured by 1 H-MRS, by 3-fold, and elevated plasma IL-6 and TNF-α levels by 40%. Diet-induced obesity caused inflammation in heart and increased macrophage-specific CD68 levels by 5-fold (Fig. 1) (* P < 0.05 vs Chow). Diet-induced cardiac inflammation was associated with significant increases in toll-like receptor 4 (TLR4) and MyD88 levels in heart (Fig. 2). HFD also increased cardiomyocyte SOCS3 levels by more than 3-fold (Fig. 3). Myocardial glucose metabolism was measured using intravenous injection of 2-[ 14 C]deoxyglucose in awake mice (n = 6). Chronic HFD reduced myocardial glucose uptake by 50%, and this was associated with significant reductions in total GLUT4 and GLUT1 protein levels. Further, Thr 172 phosphorylation of AMPK, a critical regulator of energy balance, was markedly reduced in heart following HFD (Fig. 4). These results demonstrate that diet-induced obesity causes macrophage infiltration and inflammation in heart by increasing TLR4 signaling in cardiomyocytes. Similar to the effects of inflammation on peripheral glucose metabolism, diet-induced cardiac inflammation reduced myocardial glucose metabolism by downregulating AMPK and GLUT protein levels. Thus, our findings underscore an important role of inflammation in diabetic heart.


2007 ◽  
Vol 128 (5-6) ◽  
pp. 409-411 ◽  
Author(s):  
Almut Nebel ◽  
Friederike Flachsbart ◽  
Arne Schäfer ◽  
Michael Nothnagel ◽  
Susanna Nikolaus ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Monica Molteni ◽  
Sabrina Gemma ◽  
Carlo Rossetti

Toll-like receptor 4 (TLR4) belongs to the family of pattern recognition receptors (PRRs). They are highly conserved receptors that recognize conserved pathogen-associated molecular patterns (PAMPs), thus representing the first line of defense against infections. TLR4 has been long recognized as the sensing receptor for gram-negative lipopolysaccharide (LPS). In addition, it also binds endogenous molecules produced as a result of tissue injury. Hence, TLR4 represents a key receptor on which both infectious and noninfectious stimuli converge to induce a proinflammatory response. TLR4-mediated inflammation, triggered by exogenous or endogenous ligands, is also involved in several acute and chronic diseases, having a pivotal role as amplifier of the inflammatory response. This review focuses on the research progress about the role of TLR4 activation in infectious and noninfectious (e.g., sterile) inflammation and the effects of TLR4 signaling in some pathological conditions.


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