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T-bet-Mediated Tim-3 Expression Dampens Monocyte Function During Chronic Hepatitis C Virus InfectionYi, Wenjing, Zhang, Peixin, Liang, Yan, Zhou, Yun, Shen, Huanjun, Fan, Chao, Moorman, Jonathan P., Yao, Zhi, Jia, Zhansheng, Zhang, Ying 01 March 2017 (has links)
Hepatitis C virus (HCV) induces a high rate of chronic infection via dysregulation of host immunity. We have previously shown that T-cell immunoglobulin and mucin domain protein-3 (Tim-3) is up-regulated on monocyte/macrophages (M/Mφ) during chronic HCV infection; little is known, however, about the transcription factor that controls its expression in these cells. In this study, we investigated the role of transcription factor, T-box expressed in T cells (T-bet), in Tim-3 expression in M/Mφ in the setting of HCV infection. We demonstrate that T-bet is constitutively expressed in resting CD14+ M/Mφ in the peripheral blood. M/Mφ from chronically HCV-infected individuals exhibit a significant increase in T-bet expression that positively correlates with an increased level of Tim-3 expression. Up-regulation of T-bet is also observed in CD14+ M/Mφ incubated with HCV+ Huh7.5 cells, as well as in primary M/Mφ or monocytic THP-1 cells exposed to HCV core protein in vitro, which is reversible by blocking HCV core/gC1qR interactions. Moreover, the HCV core-induced up-regulation of T-bet and Tim-3 expression in M/Mφ can be abrogated by incubating the cells with SP600125 – an inhibitor for the c-Jun N-terminal kinase (JNK) signalling pathway. Importantly, silencing T-bet gene expression decreases Tim-3 expression and enhances interleukin-12 secretion as well as signal transducer and activator of transcription 1 phosphorylation. These data suggest that T-bet, induced by the HCV core/gC1qR interaction, enhances Tim-3 expression via the JNK pathway, leading to dampened M/Mφ function during HCV infection. These findings reveal a novel mechanism for Tim-3 regulation via T-bet during HCV infection, providing new targets to combat this global epidemic viral disease.
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Monocyte subtype counts are associated with 10-year cardiovascular disease risk as determined by the Framingham Risk Score among subjects of the LIFE-Adult studyZeynalova, Samira, Bucksch, Karolin, Scholz, Markus, Yahiaoui-Doktor, Maryam, Gross, Melanie, Löffler, Markus, Melzer, Susanne, Tárnok, Attila 14 February 2022 (has links)
Coronary heart disease, an inflammatory disease, is the leading cause of death globally. White blood cell counts (including monocytes) are easily available biomarkers of systemic inflammation. Monocyte subtypes can be measured by flow cytometry and classified into classical (CD14high, CD16neg), intermediate (CD14high, CD16+) and non-classical (CD14+, CD16high) with distinct functional properties. The goal of this study was to investigate the association of monocyte total count and its subtypes with cardiovascular risk groups defined by the Framingham Risk Score, which is used to estimate the 10-year risk of developing myocardial infarction or predict mortality following coronary heart disease. We also aimed to investigate whether monocyte counts are associated with relevant cardiovascular risk factors not included in the Framingham Risk Score, such as carotid atherosclerotic plaque and intima-media thickness. Our data came from the LIFE-Adult study, a population-based cohort study of 10,000 randomly selected participants in Leipzig, Germany. Data was gathered using self-administered questionnaires and physical examinations. Carotid plaques and intima-media thickness were measured using carotid artery sonography. Monocyte subtypes in blood were determined by 10-color flow cytometry for a total of 690 individuals. In a multivariate regression analysis adjusting for the risk factors BMI, intima-media thickness, presence of carotid plaques and diabetes mellitus, monocyte subtypes and total count were found to be significantly associated with the dichotomized Framingham Risk Score (≥10% versus <10%): Odds ratios [95% confidence interval] for monocyte subtypes: classical: 11.19 [3.79–34.26]; intermediate: 2.27 [1.11–4.71]; non-classical: 4.18 [1.75–10.20]; total: 14.59 [4.61–47.95]. In absence of prospective data, the FRS was used as a surrogate for CHD. Our results indicate that monocyte counts could provide useful predictive value for cardiovascular disease risk.
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TLR4 Stimulation Induces SLAMF9-Mediated Regulation of Cytokine Production and Ras SignalingLucas, Elizabeth A. 26 May 2020 (has links)
No description available.
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d-Alanylation of Lipoteichoic Acids in Streptococcus suis Reduces Association With Leukocytes in Porcine BloodÖhlmann, Sophie, Krieger, Ann-Kathrin, Gisch, Nicolas, Meurer, Marita, de Buhr, Nicole, von Köckritz-Blickwede, Maren, Schütze, Nicole, Baums, Christoph Georg 07 June 2023 (has links)
Streptococcus suis (S. suis) is a common swine pathogen but also poses a threat to human
health in causing meningitis and severe cases of streptococcal toxic shock-like syndrome
(STSLS). Therefore, it is crucial to understand how S. suis interacts with the host immune
system during bacteremia. As S. suis has the ability to introduce d-alanine into its lipoteichoic
acids (LTAs), we investigated the working hypothesis that cell wall modification by LTA
d-alanylation influences the interaction of S. suis with porcine blood immune cells. We created
an isogenic mutant of S. suis strain 10 by in-frame deletion of the d-alanine d-alanyl carrier
ligase (DltA). d-alanylation of LTAs was associated with reduced phagocytosis of S. suis by
porcine granulocytes, reduced deposition of complement factor C3 on the bacterial surface,
increased hydrophobicity of streptococci, and increased resistance to cationic antimicrobial
peptides (CAMPs). At the same time, survival of S. suis was not significantly increased by
LTA d-alanylation in whole blood of conventional piglets with specific IgG. However, we found
a distinct cytokine pattern as IL-1β but not tumor necrosis factor (TNF)-α levels were
significantly reduced in blood infected with the ΔdltA mutant. In contrast to TNF-α, activation
and secretion of IL-1β are inflammasome-dependent, suggesting a possible influence of LTA
d-alanylation on inflammasome regulation. Especially in the absence of specific antibodies,
the association of S. suis with porcine monocytes was reduced by d-alanylation of its LTAs.
This dltA-dependent phenotype was also observed with a non-encapsulated dltA double
mutant indicating that it is independent of capsular polysaccharides. High antibody levels
caused high levels of S. suis—monocyte—association followed by inflammatory cell death
and strong production of both IL-1β and TNF-α, while the influence of LTA d-alanylation of
the streptococci became less visible. In summary, the results of this study expand previous
findings on d-alanylation of LTAs in S. suis and suggest that this pathogen specifically
modulates association with blood leukocytes through this modification of its surface.
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Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus InfectionBosteels, Cedric, Neyt, Katrijn, Vanheerswynghels, Manon, van Helden, Mary J., Sichien, Dorine, Debeuf, Nincy, De Prijck, Sofie, Bosteels, Victor, Vandamme, Niels, Martens, Liesbet, Saeys, Yvan, Louagie, Els, Lesage, Manon, Williams, David L., Tang, Shiau Choot, Mayer, Johannes U., Ronchese, Franca, Scott, Charlotte L., Hammad, Hamida, Guilliams, Martin, Lambrecht, Bart N. 16 June 2020 (has links)
The dichotomy between type 1 and 2 conventional DCs under steady-state conditions is well defined. Bosteels et al. demonstrate that, upon inflammation, cDC2s acquire a hybrid inf-cDC2 phenotype, sharing phenotype, gene expression, and function with cDC1s and monocyte-derived cells, to optimally boost CD4 and CD8 immunity via Fc receptors.
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THE IMPACT OF DIRECT-ACTING ANTI-VIRAL THERAPY ON NAIVE CD4+ T CELL LYMPHOPENIA AND CELLULAR IMMUNE ACTIVATION IN HCV INFECTION AND HCV/HIV CO-INFECTIONAuma, Ann Winniefred Nangobi 30 August 2021 (has links)
No description available.
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Interleukin-1 signaling in the stressed CNS: From microglial source to neuronal destinationDiSabato, Damon J. January 2021 (has links)
No description available.
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Circulating Monocyte Chemoattractant Protein-1 in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction Treated with Mild Hypothermia: A Biomarker Substudy of SHOCK-COOL TrialCheng, Wenke, Fuernau, Georg, Desch, Steffen, Freund, Anne, Feistritzer, Hans-Josef, Pöss, Janine, Buettner, Petra, Thiele, Holger 05 December 2023 (has links)
Background: There is evidence that monocyte chemoattractant protein-1 (MCP-1) levels
reflect the intensity of the inflammatory response in patients with cardiogenic shock (CS) complicating
acute myocardial infarction (AMI) and have a predictive value for clinical outcomes. However, little
is known about the effect of mild therapeutic hypothermia (MTH) on the inflammatory response in
patients with CS complicating AMI. Therefore, we conducted a biomarker study to investigate the
effect of MTH on MCP-1 levels in patients with CS complicating AMI. Methods: In the randomized
mild hypothermia in cardiogenic shock (SHOCK-COOL) trial, 40 patients with CS complicating
AMI were enrolled and assigned to MTH (33 ◦C) for 24 h or normothermia at a 1:1 ratio. Blood
samples were collected at predefined time points at the day of admission/day 1, day 2 and day 3.
Differences in MCP-1 levels between and within the MTH and normothermia groups were assessed.
Additionally, the association of MCP-1 levels with the risk of all-cause mortality at 30 days was
analyzed. Missing data were accounted for by multiple imputation as sensitivity analyses. Results:
There were differences in MCP-1 levels over time between patients in MTH and normothermia groups
(P for interaction = 0.013). MCP-1 levels on day 3 were higher than on day 1 in the MTH group
(day 1 vs day 3: 21.2 [interquartile range, 0.25–79.9] vs. 125.7 [interquartile range, 87.3–165.4] pg/mL;
p = 0.006) and higher than in the normothermia group at day 3 (MTH 125.7 [interquartile range,
87.3–165.4] vs. normothermia 12.3 [interquartile range, 0–63.9] pg/mL; p = 0.011). Irrespective of
therapy, patients with higher levels of MCP-1 at hospitalization tended to have a decreased risk of
all-cause mortality at 30 days (HR, 2.61; 95% CI 0.997–6.83; p = 0.051). Conclusions: The cooling
phase of MTH had no significant effect on MCP-1 levels in patients with CS complicating AMI
compared to normothermic control, whereas MCP-1 levels significantly increased after rewarming.
Trial registration: NCT01890317.
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I. Differential gene expression in human peripheral blood monocytes and alveolar macrophages II. Macrophage colony-stimulating factor is important in the development of pulmonary fibrosisOpalek, Judy Marcus 16 February 2004 (has links)
No description available.
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Lipopolysaccharide in marine bathing water : a potential real-time biomarker of bacterial contamination and relevance to human healthSattar, Anas Akram January 2014 (has links)
The quality of marine bathing water is currently assessed by monitoring the levels of faecal indicator bacteria. Among other drawbacks, results are retrospective using the traditional culture based methods. A rapid method is thus needed as an early warning to bathers for bacterial contamination in marine bathing waters. Total lipopolysaccharide (LPS) was chosen here as a potential general biomarker for bacterial contamination. Levels of total LPS, measured using a Kinetic QCL™ Limulus Amebocyte Lysate (LAL) assay, highly correlated with enumerated Escherichia coli and Bacteroides species. Levels of LPS in excess of 50 EU mL-1 were found to equate with water that was unsuitable for bathing under the current European Union regulations. Results showed that monitoring the levels of total LPS has a potential applicability as a rapid method for screening the quality of marine bathing water. More importantly, the LAL assay overcome the retrospective results when using culture based assessment since the LAL assay takes less than 30 minutes. Although false positive events were not detected, the occurrence of a false positive has been hypothesised, hence a more specific faecal biomarker was also investigated. LPS of five Bacteroides species (B. fragilis, B. caccae, B. ovatus, B. xylanisolvens and B. finegoldii) isolated from marine bathing waters samples were successfully profiled and showed high similarity between isolates in LPS gel electrophoresis banding pattern. Similar results were shown when investigating the endotoxic activity of Bacteroides species with the Kinetic QCL™ LAL assay. The potential biological relevance of Bacteroides LPS was also investigated in cell culture models indicating that Bacteroides showed similar induction of proinflammatory cytokines (TNF-α, IL-6 and IL-1α) and generally the biological activity was approximately 100 fold less than E. coli LPS. In addition, an ELISA assay was designed for the detection of Bacteroides LPS. Results showed that the Bacteroides LPS has a high potential to be used as a faecal biomarker, however, further work is required to develop a fully functional assay. The potential biological relevance of LPS present in contaminated bathing waters was also investigated in cell culture models. Results showed that there is a significant difference in the production of proinflammatory cytokines in comparison to “clean” bathing waters. Thus, results suggest that the European Directive regulations should be extended to cover the levels of total LPS in bathing waters to assure safety to the users of marine recreational water.
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