PPE11 of Mycobacterium tuberculosis can alter host inflammatory response and trigger cell death

2019 ◽  
Vol 126 ◽  
pp. 45-55 ◽  
Author(s):  
Xuan Peng ◽  
Tao Luo ◽  
Xiaoqian Zhai ◽  
Chunxi Zhang ◽  
Jing Suo ◽  
...  
Keyword(s):  
Cell Death ◽  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Trigger Cell Death ◽  
Host Inflammatory Response

scholarly journals Integrative Analysis of Human Macrophage Inflammatory Response Related to Mycobacterium tuberculosis Virulence

2021 ◽  
Vol 12 ◽  
Author(s):  
Pauline Bade ◽  
Fabrizio Simonetti ◽  
Stephanie Sans ◽  
Patricia Laboudie ◽  
Khadija Kissane ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Genetic Networks ◽  
Host Cells ◽  
Human Macrophage ◽  
Human Macrophages ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Main Host ◽  
Host Inflammatory Response

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, kills 1.5 to 1.7 million people every year. Macrophages are Mtb’s main host cells and their inflammatory response is an essential component of the host defense against Mtb. However, Mtb is able to circumvent the macrophages’ defenses by triggering an inappropriate inflammatory response. The ability of Mtb to hinder phagolysosome maturation and acidification, and to escape the phagosome into the cytosol, is closely linked to its virulence. The modulation of the host inflammatory response relies on Mtb virulence factors, but remains poorly studied. Understanding macrophage interactions with Mtb is crucial to develop strategies to control tuberculosis. The present study aims to determine the inflammatory response transcriptome and miRNome of human macrophages infected with the virulent H37Rv Mtb strain, to identify macrophage genetic networks specifically modulated by Mtb virulence. Using human macrophages infected with two different live strains of mycobacteria (live or heat-inactivated Mtb H37Rv and M. marinum), we quantified and analyzed 184 inflammatory mRNAs and 765 micro(mi)RNAs. Transcripts and miRNAs differently modulated by H37Rv in comparison with the two other conditions were analyzed using in silico approaches. We identified 30 host inflammatory response genes and 37 miRNAs specific for H37Rv virulence, and highlight evidence suggesting that Mtb intracellular-linked virulence depends on the inhibition of IL-1β-dependent pro-inflammatory response, the repression of apoptosis and the delay of the recruitment and activation of adaptive immune cells. Our findings provide new potential targets for the development of macrophage-based therapeutic strategies against TB.

scholarly journals Aggregated Mycobacterium tuberculosis enhances the inflammatory response

2021 ◽  
Author(s):  
Alex Sigal ◽  
Hylton Rodel ◽  
Isabella Markham Ferreira ◽  
Carly Ziegler ◽  
Yasica Ganga ◽  
...  
Keyword(s):  
Cell Death ◽  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Host Cell ◽  
Human Lung ◽  
Transcriptional Response ◽  
Human Macrophage ◽  
Cell Infection ◽  
Host Cell Death ◽  
Nfκb Pathway

Mycobacterium tuberculosis (Mtb) readily aggregates in culture and Mtb aggregates in the lung were observed in experimental Mtb infection. However, the physiological consequences of Mtb aggregation are incompletely understood. Here we examined the human macrophage transcriptional response to aggregated Mtb relative to infection with non-aggregated single or multiple bacilli per host cell. Infection with aggregated Mtb led to an early upregulation of pro-inflammatory associated genes and enhanced TNFα signaling via the NFκB pathway. Both these pathways were significantly upregulated relative to infection with single bacilli, and TNFα signaling was also significantly elevated relative to infection with multiple non-aggregated Mtb. Secretion of TNFα and downstream cytokines were also enhanced. On a longer timescale, aggregate infection led to overall increased acidification per macrophage and a high proportion of death in these cells after aggregate phagocytosis. Host cell death did not occur when Mtb aggregates were heat killed despite such clumps being readily picked up. To validate that Mtb aggregates do occur in the human lung, we document Mtb aggregates surrounding a cavity in a human TB lesion. Aggregates may therefore be present in some lesions and elicit a stronger inflammatory response resulting in recruitment of additional phagocytes and their subsequent death, potentially leading to necrosis and transmission.

Inhibition of Autophagy Potentiated Hippocampal Cell Death Induced by Endoplasmic Reticulum Stress and its Activation by Trehalose Failed to be Neuroprotective

2019 ◽  
Vol 16 (1) ◽  
pp. 3-11
Author(s):  
Luisa Halbe ◽  
Abdelhaq Rami
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Cell Damage ◽  
Protective Mechanism ◽  
Unfolded Proteins ◽  
Neuronal Viability ◽  
Hippocampal Cell ◽  
Trigger Cell Death ◽  
Autophagy Inhibition

Introduction: Endoplasmic reticulum (ER) stress induced the mobilization of two protein breakdown routes, the proteasomal- and autophagy-associated degradation. During ERassociated degradation, unfolded ER proteins are translocated to the cytosol where they are cleaved by the proteasome. When the accumulation of misfolded or unfolded proteins excels the ER capacity, autophagy can be activated in order to undertake the degradative machinery and to attenuate the ER stress. Autophagy is a mechanism by which macromolecules and defective organelles are included in autophagosomes and delivered to lysosomes for degradation and recycling of bioenergetics substrate. Materials and Methods: Autophagy upon ER stress serves initially as a protective mechanism, however when the stress is more pronounced the autophagic response will trigger cell death. Because autophagy could function as a double edged sword in cell viability, we examined the effects autophagy modulation on ER stress-induced cell death in HT22 murine hippocampal neuronal cells. We investigated the effects of both autophagy-inhibition by 3-methyladenine (3-MA) and autophagy-activation by trehalose on ER-stress induced damage in hippocampal HT22 neurons. We evaluated the expression of ER stress- and autophagy-sensors as well as the neuronal viability. Results and Conclusion: Based on our findings, we conclude that under ER-stress conditions, inhibition of autophagy exacerbates cell damage and induction of autophagy by trehalose failed to be neuroprotective.

scholarly journals AB0713 PERIODONTAL DISEASES AND ITS ASSOCIATION WITH ANKYLOSING SPONDYLITIS/SPA: A SYSTEMATIC REVIEW

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1652.1-1652
Author(s):  
A. Pandey ◽  
V. Ravindran ◽  
M. Pandey ◽  
R. Rajak ◽  
V. Pandey
Keyword(s):  
Systematic Review ◽  
Ankylosing Spondylitis ◽  
Connective Tissue ◽  
Inflammatory Response ◽  
Periodontal Disease ◽  
Close Association ◽  
Case Control ◽  
Clinical Attachment Loss ◽  
Tnf Α ◽  
Host Inflammatory Response

Background:A close association between periodontal disease and Ankylosing spondylitis (AS) has long been specualted. Both diseases are characterized by dysregulation of the host inflammatory response, leading to further destruction of soft and hard connective tissue with there being evidence of increased levels of TNF-α and various interleukins in both patients of AS and periodontitis.Objectives:The aim of this systematic review was to appraise the available literature exploring the relationship between AS and periodontal disease.Methods:We searched Medline & Embase databases (from their inception till October 2019) using appropriate combinations of following search items with limits ‘(English, Human)’; Ankylosing spondylitis, spondyloarthritis, spondyloarthropathies, spondyloarthritides, spinal disease, musculoskeletal disease, Rheumatic disease AND periodontitis, periodontal disease, periodontoses, parodontoses, chronic periodontitis, gum disease, gingivitis, oral health, dental health, plaque index, bleeding on probing, probing pocket depth, clinical attachment loss. This search was supplemented by the manual search of bibliographies of articles selected and conferences proceedings of EULAR. Only be reviews, observational study of cross-sectional, cohort or case control type on adult patients with AS were selected. Data was extracted from a predesigned proforma. A close association between periodontal disease and Ankylosing spondylitis (AS) has long been specualted. Both diseases are characterized by dysregulation of the host inflammatory response, leading to further destruction of soft and hard connective tissue with there being evidence of increased levels of TNF-α and various interleukins in both patients of AS and periodontitis.Results:A total number of 984 articles were identified and 12 were selcted for detailed appraisal (Figure 1, PRISMA flow chart). They were all case control studies. The prevalence of periodontitis ranged from 38% to 88% in patients with AS whereas in the control group from 26% to 71 % in controls. Out of 12 studies, two showed significant changes in Plaque Index (PI), two studies showed altered Pocket Probing Depth (PPD), three showed significant increased in Clinical Attachment Loss (CAL) and increased Bleeding On Probing (BOP) was seen in 2 studies. In 7 studies, periodontitis was seen in a significant number of patients with AS (P<0.05). All studies reported that the prevalence of periodontal disease in AS patients was higher as compared to non-AS patients.Conclusion:Our systematic review found an association between AS and periodontal disease. Patients with AS show higher prevalence of periodontitis and a poor oral hygiene as compared to healthy controls. At practice level, this systematic review underscores the need for a collaboration between dentists and rheumatologist.Disclosure of Interests:None declared

scholarly journals Depletion of the DarG antitoxin in Mycobacterium tuberculosis triggers the DNA‐damage response and leads to cell death

2020 ◽  
Vol 114 (4) ◽  
pp. 641-652 ◽  
Author(s):  
Anisha Zaveri ◽  
Ruojun Wang ◽  
Laure Botella ◽  
Ritu Sharma ◽  
Linnan Zhu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Mycobacterium Tuberculosis ◽  
Dna Damage Response ◽  
Damage Response

scholarly journals Short-term intense Bcr–Abl kinase inhibition with nilotinib is adequate to trigger cell death in BCR-ABL+ cells

Leukemia ◽  
2009 ◽  
Vol 23 (6) ◽  
pp. 1205-1206 ◽  
Author(s):  
D K Hiwase ◽  
D L White ◽  
V A Saunders ◽  
S Kumar ◽  
J V Melo ◽  
...  
Keyword(s):  
Cell Death ◽  
Short Term ◽  
Kinase Inhibition ◽  
Abl Kinase ◽  
Trigger Cell Death

Stilbene–Chalcone Hybrids: Design, Synthesis, and Evaluation as a New Class of Antimalarial Scaffolds That Trigger Cell Death through Stage Specific Apoptosis

2011 ◽  
Vol 55 (1) ◽  
pp. 297-311 ◽  
Author(s):  
Naina Sharma ◽  
Dinesh Mohanakrishnan ◽  
Amit Shard ◽  
Abhishek Sharma ◽  
Saima ◽  
...  
Keyword(s):  
Cell Death ◽  
Design Synthesis ◽  
New Class ◽  
Trigger Cell Death

scholarly journals Inflammasomes inMycobacterium tuberculosis-Driven Immunity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Sebastian Wawrocki ◽  
Magdalena Druszczynska
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Protein Complexes ◽  
Inflammasome Activation ◽  
Host Immune Responses ◽  
Multimeric Protein

The development of effective innate and subsequent adaptive host immune responses is highly dependent on the production of proinflammatory cytokines that increase the activity of immune cells. The key role in this process is played by inflammasomes, multimeric protein complexes serving as a platform for caspase-1, an enzyme responsible for proteolytic cleavage of IL-1βand IL-18 precursors. Inflammasome activation, which triggers the multifaceted activity of these two proinflammatory cytokines, is a prerequisite for developing an efficient inflammatory response against pathogenicMycobacterium tuberculosis(M.tb). This review focuses on the role of NLRP3 and AIM2 inflammasomes inM.tb-driven immunity.

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