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Glucocorticoid-Induced Exacerbation of Mycobacterial Infection Is Associated With a Reduced Phagocytic Capacity of Macrophages.

ABSTRACT: Glucocorticoids are effective drugs for treating immune-related diseases, but prolonged therapy is associated with an increased risk of various infectious diseases, including tuberculosis. In this study, we have used a larval zebrafish model for tuberculosis, based on Mycobacterium marinum (Mm) infection, to study the effect of glucocorticoids. Our results show that the synthetic glucocorticoid beclomethasone increases the bacterial burden and the dissemination of a systemic Mm infection. The exacerbated Mm infection was associated with a decreased phagocytic activity of macrophages, higher percentages of extracellular bacteria, and a reduced rate of infected cell death, whereas the bactericidal capacity of the macrophages was not affected. The inhibited phagocytic capacity of macrophages was associated with suppression of the transcription of genes involved in phagocytosis in these cells. The decreased bacterial phagocytosis by macrophages was not specific for Mm, since it was also observed upon infection with Salmonella Typhimurium. In conclusion, our results show that glucocorticoids inhibit the phagocytic activity of macrophages, which may increase the severity of bacterial infections like tuberculosis.

SUBMITTER: Xie Y

PROVIDER: S-EPMC8148013 | biostudies-literature |

REPOSITORIES: biostudies-literature

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HIV infection is associated with reduced pulmonary diffusing capacity.

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Human Hookworm Infection Enhances Mycobacterial Growth Inhibition and Associates With Reduced Risk of Tuberculosis Infection.

Project description:Soil-transmitted helminths and Mycobacterium tuberculosis frequently coincide geographically and it is hypothesized that gastrointestinal helminth infection may exacerbate tuberculosis (TB) disease by suppression of Th1 and Th17 responses. However, few studies have focused on latent TB infection (LTBI), which predominates globally. We performed a large observational study of healthy adults migrating from Nepal to the UK (n = 645). Individuals were screened for LTBI and gastrointestinal parasite infections. A significant negative association between hookworm and LTBI-positivity was seen (OR = 0.221; p = 0.039). Hookworm infection treatment did not affect LTBI conversions. Blood from individuals with hookworm had a significantly greater ability to control virulent mycobacterial growth in vitro than from those without, which was lost following hookworm treatment. There was a significant negative relationship between mycobacterial growth and eosinophil counts. Eosinophil-associated differential gene expression characterized the whole blood transcriptome of hookworm infection and correlated with improved mycobacterial control. These data provide a potential alternative explanation for the reduced prevalence of LTBI among individuals with hookworm infection, and possibly an anti-mycobacterial role for helminth-induced eosinophils.

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Human hookworm infection enhances mycobacterial growth inhibition and associates with reduced risk of tuberculosis infection.

Project description:Soil-transmitted helminths and Mycobacterium tuberculosis frequently coincide geographically and it is hypothesized that gastrointestinal helminth infection may exacerbate tuberculosis (TB) disease by suppression of Th1 and Th17 responses. However, few studies have focused on latent TB (LTBI) infection, which predominates globally. We performed a large observational study of healthy adults migrating from Nepal to the UK (n=645). Individuals were screened for LTBI and gastrointestinal parasite (GIP) infections. A significant negative association between hookworm (HW) and LTBI-positivity was seen (OR=0.221; p=0.039). HW treatment did not effect LTBI conversions. Blood from individuals with HW had a significantly greater ability to control virulent mycobacterial growth in vitro than from those without, which was lost following HW treatment. There was a significant negative relationship between mycobacterial growth and eosinophil counts. We also analysed differential gene expression among individuals with and without HW infection, pre- and post- anti-helminth treatment. Eosinophil-associated differential gene expression characterised the whole blood transcriptome of hookworm infection and correlated with improved mycobacterial control. These data provide a potential alternative explanation for the reduced prevalence of LTBI among individuals with HW infection, and possibly an anti-mycobacterial role for helminth-induced eosinophils.

2018-12-26 | GSE122737 | GEO

Weighted Gene Co-Expression Network Analysis Identifies Key Modules and Hub Genes Associated with Mycobacterial Infection of Human Macrophages.

Project description:Tuberculosis (TB) is still a leading cause of death worldwide. Treatments remain unsatisfactory due to an incomplete understanding of the underlying host-pathogen interactions during infection. In the present study, weighted gene co-expression network analysis (WGCNA) was conducted to identify key macrophage modules and hub genes associated with mycobacterial infection. WGCNA was performed combining our own transcriptomic results using Mycobacterium aurum-infected human monocytic macrophages (THP1) with publicly accessible datasets obtained from three types of macrophages infected with seven different mycobacterial strains in various one-to-one combinations. A hierarchical clustering tree of 11,533 genes was built from 198 samples, and 47 distinct modules were revealed. We identified a module, consisting of 226 genes, which represented the common response of host macrophages to different mycobacterial infections that showed significant enrichment in innate immune stimulation, bacterial pattern recognition, and leukocyte chemotaxis. Moreover, by network analysis applied to the 74 genes with the best correlation with mycobacteria infection, we identified the top 10 hub-connecting genes: NAMPT, IRAK2, SOCS3, PTGS2, CCL20, IL1B, ZC3H12A, ABTB2, GFPT2, and ELOVL7. Interestingly, apart from the well-known Toll-like receptor and inflammation-associated genes, other genes may serve as novel TB diagnosis markers and potential therapeutic targets.

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Glucocorticoid-Induced Hyperglycemia Including Dexamethasone-Associated Hyperglycemia in COVID-19 Infection: A Systematic Review.

Project description:ObjectiveOptimal glucocorticoid-induced hyperglycemia (GCIH) management is unclear. The COVID-19 pandemic has made this issue more prominent because dexamethasone became the standard of care in patients needing respiratory support. This systematic review aimed to describe the management of GCIH and summarize available management strategies for dexamethasone-associated hyperglycemia in patients with COVID-19.MethodsA systematic review was conducted using the PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases with results from 2011 through January 2022. Keywords included synonyms for "steroid-induced diabetes" or "steroid-induced hyperglycemia." Randomized controlled trials (RCTs) were included for review of GCIH management. All studies focusing on dexamethasone-associated hyperglycemia in COVID-19 were included regardless of study quality.ResultsInitial search for non-COVID GCIH identified 1230 references. After screening and review, 33 articles were included in the non-COVID section of this systematic review. Initial search for COVID-19-related management of dexamethasone-associated hyperglycemia in COVID-19 identified 63 references, whereas 7 of these were included in the COVID-19 section. RCTs of management strategies were scarce, did not use standard definitions for hyperglycemia, evaluated a variety of treatment strategies with varying primary end points, and were generally not found to be effective except for Neutral Protamine Hagedorn insulin added to basal-bolus regimens.ConclusionFew RCTs are available evaluating GCIH management. Further studies are needed to support the formulation of clinical guidelines for GCIH especially given the widespread use of dexamethasone during the COVID-19 pandemic.

| S-EPMC9354392 | biostudies-literature

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