Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome

Tan, Hui; Yong, Yean Kong; Shankar, Esaki Muthu; Paukovics, Geza; Ellegård, Rada; Larsson, Marie; Kamarulzaman, Adeeba; French, Martyn A.; Crowe, Suzanne

doi:10.4049/jimmunol.1502203

Cited by 65 publications

(55 citation statements)

References 65 publications

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“…Similar to earlier time points, neutrophil-dependent inflammatory responses (MMP9, CTSG, and LCN2) continued to be transcriptionally up-regulated ( Table S3 ) in patients with TBM-IRIS. Inflammasome activation has recently been shown as an important mediator of tuberculosis-IRIS in 2 independent studies [9, 11]. In accordance with these results, functional analysis of the differentially abundant transcript also indicated significant up-regulation of transcripts associated with inflammasome activation (Figure 3B).…”

Section: Resultssupporting

confidence: 83%

“…We have previously shown that Toll-like receptor signaling and inflammasome activation are key mediators of dysregulated cytokine production in a cohort of patients with heterogenous presentations of paradoxical tuberculosis-IRIS [9]. Most recently, Tan and colleagues [11] have also reported that monocytes from patients with tuberculosis-IRIS displayed aberrant inflammasome activation and had greater cell death both before and after ART. …”

Section: Discussionmentioning

confidence: 99%

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Inflammasome activation underlies central nervous system deterioration in HIV-associated tuberculosis

et al. 2016

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Tuberculous meningitis (TBM) is a frequent cause of meningitis in individuals with human immunodeficiency virus (HIV) infection, resulting in death in approximately 40% of affected patients. A severe complication of antiretroviral therapy (ART) in these patients is neurological tuberculosis–immune reconstitution inflammatory syndrome (IRIS), but its underlying cause remains poorly understood. To investigate the pathogenesis of TBM-IRIS, we performed longitudinal whole-blood microarray analysis of HIV-infected patients with TBM and reflected the findings at the protein level. Patients in whom TBM-IRIS eventually developed had significantly more abundant neutrophil-associated transcripts, from before development of TBM-IRIS through IRIS symptom onset. After ART initiation, a significantly higher abundance of transcripts associated with canonical and noncanonical inflammasomes was detected in patients with TBM-IRIS than in non-IRIS controls. Whole-blood transcriptome findings complement protein measurement from the site of disease, which together suggest a dominant role for the innate immune system in the pathogenesis of TBM-IRIS.

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Section: Resultssupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Inflammasome activation underlies central nervous system deterioration in HIV-associated tuberculosis

et al. 2016

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“…Although initiation of ART during treatment of TBM is associated with a reduced 6 mo mortality (HR 0.3, 95% CI = 0.08–0.82) IRIS in this context carries a poor prognosis with one study reporting a mortality rate of 25% with severe disability at 9 mo observed in 23% of those who survived . The role of inflammasomes, immune complexes of receptors, and sensors that mediate innate immune responses and lead to inflammation, have been described in this setting …”

Section: Differences In the Intracerebral Immune Response In The Hiv‐mentioning

confidence: 99%

The pathogenesis of tuberculous meningitis

Davis

Rohlwink

Proust

et al. 2019

Journal of Leukocyte Biology

139

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Tuberculosis (TB) remains a leading cause of death globally. Dissemination of TB to the brain results in the most severe form of extrapulmonary TB, tuberculous meningitis (TBM), which represents a medical emergency associated with high rates of mortality and disability. Via various mechanisms the Mycobacterium tuberculosis (M.tb) bacillus disseminates from the primary site of infection and overcomes protective barriers to enter the CNS. There it induces an inflammatory response involving both the peripheral and resident immune cells, which initiates a cascade of pathologic mechanisms that may either contain the disease or result in significant brain injury. Here we review the steps from primary infection to cerebral disease, factors that contribute to the virulence of the organism and the vulnerability of the host and discuss the immune response and the clinical manifestations arising. Priorities for future research directions are suggested. K E Y W O R D S mycobacterial, endothelial cells, granulocytes, microglia cells, monocytes/macrophages, myeloid cells, neutrophils, T Lymphocytes, Th17 cells at the site of infection activates macrophages and DCs to produce cytokines and antimicrobial factors that contribute to containment of the TB bacillus. 2 This inflammatory process results in the formation of a granuloma, which encapsulates the infected cells and retards the replication of TB bacilli and can lead to latent infection. However, in

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“…A higher frequency of HBsAg loss has been associated with lower CD4+ T cell count prior to initiation of HBV-active ART [114, 115, 117] and a greater increase in CD4+ T-cells following ART [115, 118] but many of these studies were retrospective or didn’t include individuals with low CD4+ T-cells prior to ART. The relationship between low CD4+ T-cell count and enhanced HBsAg loss and seroconversion may potentially be secondary to brisk immune reconstitution that has been associated with high levels of IL18 production which could enhance dendritic cell function, adaptive immunity and antibody production [119] .…”

Section: Natural History Of Hiv-hbv Co-infection In the Era Of Hbvmentioning

confidence: 99%

HIV-hepatitis B virus coinfection

Singh¹,

Crane

Audsley

et al. 2017

Aids

191

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HIV infection has a significant impact on the natural history of chronic HBV infection, with increased levels of HBV DNA, accelerated progression of liver disease and increased liver-associated mortality compared to HBV mono-infection. Widespread uptake and early initiation of HBV-active antiretroviral therapy (ART) has substantially improved the natural history of HIV-HBV co-infection but the prevalence of liver disease remains elevated in this population. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease and seroconversion in HIV-HBV co-infection in the era of HBV-active ART and the effects of HIV directly on liver disease. We also review novel therapeutics for the management of HBV with a particular emphasis on clinical strategies being developed for an HBV cure and an HIV cure and their impact on HIV-HBV co-infected individuals.

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Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome

Cited by 65 publications

References 65 publications

Inflammasome activation underlies central nervous system deterioration in HIV-associated tuberculosis

Inflammasome activation underlies central nervous system deterioration in HIV-associated tuberculosis

The pathogenesis of tuberculous meningitis

HIV-hepatitis B virus coinfection

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