Plasma Proinflammatory Cytokines Are Markers of Disease Severity and Bacterial Burden in Pulmonary Tuberculosis

Kumar, Nathella Pavan; Moideen, Kadar; Banurekha, Vaithilingam V.; Nair, Dina; Babu, Subash

doi:10.1093/ofid/ofz257

Cited by 74 publications

(82 citation statements)

References 31 publications

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“…We found that EPA/DHA therapy lowered the pro-inflammatory plasma cytokines IL-1β and TNF-α as well as lung IL-1α and IFN-γ. This is in congruence with the lower bacterial load [45] and a more pro-resolving lung LM profile found in the EPA/DHA group, resulting from changes in the FA composition evident in all FA pools measured. In contrast to these findings, iron supplementation resulted in a higher n-6 LCPUFA composition of PBMCs and lung tissue membranes.…”

Section: Discussionsupporting

confidence: 83%

“…Improvements in inflammation mediated the improvements in the biomarkers of iron status and anemia of infection in the EPA/DHA and Fe groups. Mutually, TNF-α, IFN-γ, and IL-1 are important in host defense against TB, but higher concentrations of these markers have also been associated with worsened lung pathology together with disease severity [43][44][45]. We found that EPA/DHA therapy lowered the pro-inflammatory plasma cytokines IL-1β and TNF-α as well as lung IL-1α and IFN-γ.…”

Section: Discussionmentioning

confidence: 62%

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Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice

et al. 2020

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Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in Mycobacterium tuberculosis-infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1β, and TNF-α. Fe lowered lung IL-1α, IL-1β, plasma IL-1β, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 62%

Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice

et al. 2020

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“…High concentrations of cytokines and chemokines were required for early protection against Mtb infections [13]. Plasma cytokines also could be biomarkers of disease severity, and relieve mycobacterial burden in PTB [14]. Our results consistent with report that PTB individuals displayed significantly elevated levels of CCL1, CCL3, CXCL1, CXCL10 and CXCL11 as bacterial burdens dependent.…”

Section: Discussionsupporting

confidence: 90%

“…Our results consistent with report that PTB individuals displayed significantly elevated levels of CCL1, CCL3, CXCL1, CXCL10 and CXCL11 as bacterial burdens dependent. The chemokines were significantly reduced following successful treatment [14].…”

Section: Discussionmentioning

confidence: 97%

Gene network in pulmonary tuberculosis based on bioinformatic analysis

Lyu

et al. 2020

Preprint

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Background: Pulmonary tuberculosis (PTB) is one of the serious infectious diseases worldwide; however, the gene network involved in the host response remain largely unclear. Methods: This study integrated two cohorts profile datasets GSE34608 and GSE83456 to elucidate the potential gene network and signaling pathways in PTB. Differentially expressed genes (DEGs) were obtained for Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using Metascape database. Protein-Protein Interaction (PPI) network of DEGs was constructed by the online database the Search Tool for the Retrieval of Interacting Genes (STRING). Modules were identified by the plug-in APP Molecular Complex Detection (MCODE) in Cytoscape. GO and KEGG pathway of Module 1 were further analyzed by STRING. Hub genes were selected for further expression validation in dataset GSE19439. The gene expression level was also investigated in the dataset GSE31348 to display the change pattern during the PTB treatment. Results: Totally, 180 shared DEGs were identified from two datasets. Gene function and KEGG pathway enrichment revealed that DEGs mainly enriched in defense response to other organism, response to bacterium, myeloid leukocyte activation, cytokine production, etc. Seven modules were clustered based on PPI network. Module 1 contained 35 genes related to cytokine associated functions, among which 14 genes, including chemokine receptors, interferon-induced proteins and Toll-like receptors, were identified as hub genes. Expression levels of the hub genes were validated with a third dataset GSE19439. The signature of this core gene network showed significant response to Mycobacterium tuberculosis (Mtb) infection, and correlated with the gene network pattern during anti-PTB therapy. Conclusions: Our study unveils the coordination of causal genes during PTB infection, and provides a promising gene panel for PTB diagnosis. As major regulators of the host immune response to Mtb infection, the 14 hub genes are also potential molecular targets for developing PTB drugs.

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“…88,89 In contrast, boosting TH cytokine responses could serve as a feasible strategy for those with acute/recent Mtb infection. 90,91 Cytokines may polarize the immune response in favour of host protection by strengthening immune and memory responses or by disrupting and penetrating the granuloma to expose Mtb bacilli to anti-TB treatment (Table 2; Fig. 1).…”

Section: Vitamins and Biologicsmentioning

confidence: 99%

Therapeutic host-directed strategies to improve outcome in tuberculosis

2020

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Bacille Calmette-Guérin (BCG) is the only licenced tuberculosis (TB) vaccine, but has limited efficacy against pulmonary TB disease development and modest protection against extrapulmonary TB. Preventative antibiotic treatment for Mycobacterium tuberculosis (Mtb) infections in high-prevalence settings is unfeasible due to unclear treatment durability, drug toxicity, logistical constraints related to directly observed treatment strategy (DOTS) and the lengthy treatment protocols. Together, these factors promote nonadherence, contributing to relapse and establishment of drug-resistant Mtb strains. Although antibiotic treatment of drugsusceptible Mtb is generally effective, drug-resistant TB has a treatment efficacy below 50% and can, in a proportion, develop into progressive, untreatable disease. Other immune compromising co-infections and/or co-morbidities require more complex prevention/treatment approaches, posing huge financial burdens to national health services. Novel TB treatment strategies, such as host-directed therapeutics, are required to complement pathogen-targeted approaches. Pre-clinical studies have highlighted promising candidates that enhance endogenous pathways and/or limit destructive host responses. This review discusses promising pre-clinical candidates and forerunning compounds at advanced stages of clinical investigation in TB host-directed therapeutic (HDT) efficacy trials. Such approaches are rationalized to improve outcome in TB and shorten treatment strategies.

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Plasma Proinflammatory Cytokines Are Markers of Disease Severity and Bacterial Burden in Pulmonary Tuberculosis

Cited by 74 publications

References 31 publications

Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice

Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in Mycobacterium tuberculosis-Infected Mice

Gene network in pulmonary tuberculosis based on bioinformatic analysis

Therapeutic host-directed strategies to improve outcome in tuberculosis

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