Analysis of the immune response of human dendritic cells to Mycobacterium tuberculosis by quantitative proteomics

Kuo, Chiu-Ping; Chang, Kuo-Song; Hsu, Jue‐Liang; Tsai, I-Fang; Lin, Andrew; Wei, Tsai-Yin; Wu, Chien‐Liang; Lu, Yen‐Ta

doi:10.1186/s12953-016-0095-8

Cited by 9 publications

(7 citation statements)

References 43 publications

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“…Therefore, targeting the CD13 receptor may help reduce the ability of Mtb to inhibit T-cell activation, but the specific Mtb effectors modulating CD13 expression are currently unknown. 42 More questions remain regarding the mechanisms by which Mtb manipulates DCs and the consequences of that manipulation on the nature and kinetics of the adaptive immune responses toward Mtb.…”

Section: Dendritic Cellsmentioning

confidence: 99%

Innate immunity in tuberculosis: host defense vs pathogen evasion

2017

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The major innate immune cell types involved in tuberculosis (TB) infection are macrophages, dendritic cells (DCs), neutrophils and natural killer (NK) cells. These immune cells recognize the TB-causing pathogen Mycobacterium tuberculosis (Mtb) through various pattern recognition receptors (PRRs), including but not limited to Toll-like receptors (TLRs), Nod-like receptors (NLRs) and C-type lectin receptors (CLRs). Upon infection by Mtb, the host orchestrates multiple signaling cascades via the PRRs to launch a variety of innate immune defense functions such as phagocytosis, autophagy, apoptosis and inflammasome activation. In contrast, Mtb utilizes numerous exquisite strategies to evade or circumvent host innate immunity. Here we discuss recent research on major host innate immune cells, PRR signaling, and the cellular functions involved in Mtb infection, with a specific focus on the host's innate immune defense and Mtb immune evasion. A better understanding of the molecular mechanisms underlying host-pathogen interactions could provide a rational basis for the development of effective anti-TB therapeutics.

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Section: Dendritic Cellsmentioning

confidence: 99%

Innate immunity in tuberculosis: host defense vs pathogen evasion

2017

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“…During the last years, several MS studies were published that analyzed different cell organelles of mycobacteria-infected cells ( 48 ), such as cytoplasm and nucleus ( 26 ), the ER ( 27 ), secreted exosomes ( 28 ), plasma and cell organelle membranes ( 30 , 31 ), as well as phagosomes ( 32 – 36 ), which provide detailed insight in the cellular mechanisms of mycobacterial infection. We have listed these findings in Tables 1 B,C.…”

Section: Proteome Analysis Of Mycobacteria-containing Vacuolesmentioning

confidence: 99%

“…We have listed these findings in Tables 1 B,C. For example, in a quantitative MS approach, Kuo et al performed membrane profiling on human dendritic cells and identified 115 proteins that were upregulated in response to heat-killed Mtb ( 30 ). Among those host proteins, aminopeptidase N was found largely overexpressed, and the authors could demonstrate that membranous aminopeptidase N is capable of binding live bacteria and is involved in antigen presentation that impaired T cell activation to facilitate Mtb pathogenesis.…”

Section: Proteome Analysis Of Mycobacteria-containing Vacuolesmentioning

confidence: 99%

Proteomics of Mycobacterium Infection: Moving towards a Better Understanding of Pathogen-Driven Immunomodulation

et al. 2018

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Intracellular bacteria are responsible for many infectious diseases in humans and have developed diverse mechanisms to interfere with host defense pathways. In particular, intracellular vacuoles are an essential niche used by pathogens to alter cellular and organelle functions, which facilitate replication and survival. Mycobacterium tuberculosis (Mtb), the pathogen causing tuberculosis in humans, is not only able to modulate its intraphagosomal fate by blocking phagosome maturation but has also evolved strategies to successfully prevent clearance by immune cells and to establish long-term survival in the host. Mass spectrometry (MS)-based proteomics allows the identification and quantitative analysis of complex protein mixtures and is increasingly employed to investigate host–pathogen interactions. Major challenges are limited availability and purity of pathogen-containing compartments as well as the asymmetric ratio in protein abundance when comparing bacterial and host proteins during the infection. Recent advances in purification techniques and MS technology helped to overcome previous difficulties and enable the detailed proteomic characterization of infected host cells and their pathogen-containing vacuoles. Here, we summarize current findings of the proteomic analysis of Mycobacterium-infected host cells and highlight progress that has been made to study the protein composition of mycobacterial vacuoles. Current investigations focus on the pathogenicity during Mtb infection, which will allow to better understand pathogen-induced changes and immunomodulation of infected host cells. Consequently, future research in this field will have important implications on host response, pathogen survival, and persistence, induced adaptive immunity and metabolic changes of immune cells promoting the development of novel host-directed therapies in tuberculosis.

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“…Therefore, reduction of plasma lipids may not be fully effective at controlling latent TB. In fact, our previous study showed that another lipid-lowering agent, ezetimibe, known to inhibit cholesterol uptake into cells, was associated with a lower risk of latent TB in patients with diabetes [29][30][31]. Our current study shows that fenofibrate not only sustains the availability of intracellular lipids but also enhances dormant genes known to involved in lipid metabolism.…”

Section: Discussionmentioning

confidence: 52%

Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term Treatment

Liu

Tsai

et al. 2020

JCM

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Background: Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that infects and persists in macrophages. This study aimed to investigate the effects of long-term fenofibrate treatment in patients with tuberculosis (TB), and the intracellular viability of Mtb in human macrophages. Methods: Epidemiological data from the National Health Insurance Research Database of Taiwan were used to present outcomes of TB patients treated with fenofibrate. In the laboratory, we assessed Mtb infection in macrophages treated with or without fenofibrate. Mtb growth, lipid accumulation in macrophages, and expression of transcriptional genes were examined. Results: During 11 years of follow-up, TB patients treated with fenofibrate presented a higher risk of mortality. Longer duration of fenofibrate use was associated with a significantly higher risk of mortality. Treatment with fenofibrate significantly increased the number of bacilli in human macrophages in vitro. Fenofibrate did not reduce, but induced an increasing trend in the intracellular lipid content of macrophages. In addition, dormant genes of Mtb, icl1, tgs1, and devR, were markedly upregulated in response to fenofibrate treatment. Our results suggest that fenofibrate may facilitate intracellular Mtb persistence. Conclusions: Our data shows that long-term treatment with fenofibrate in TB patients is associated with a higher mortality. The underlying mechanisms may partly be explained by the upregulation of Mtb genes involved in lipid metabolism, enhanced intracellular growth of Mtb, and the ability of Mtb to sustain a nutrient-rich reservoir in human macrophages, observed during treatment with fenofibrate. people, it still presents the highest incidence and mortality rate [2]. This disease is transmitted via inhalation of aerosolized bacilli, which then replicate within alveolar macrophages in lung tissue. In the host, immune cells can be recruited to the affected sites, and encase the invading mycobacteria, forming a structure known as the granuloma [3,4]. A granuloma is composed of infected alveolar macrophages, monocytes, multinucleated giant cells, epithelioid cells, and most notably, foamy macrophages [4,5]. The foamy aspect of these cells results from the accumulation of neutral lipids, typically triacylglycerides and esterified and non-esterified sterols. These foamy macrophages are nutrient-rich reservoirs for Mtb persistence [6,7].Published data support that regulating cholesterol in macrophages may affect the intracellular growth of Mtb [8,9]. However, questions remain regarding the use of hypolipidemic therapy for the treatment of Mtb infection [10]. By the activation of peroxisome proliferator activated receptor α (PPARα), mainly expressed in the liver, heart, monocytes, and macrophages, fenofibrate increases lipolysis and elimination of lipids from plasma [11][12][13]. It is commonly prescribed for the treatment of hypertriglyceridemia or mixed hyperlipidemia [13][14][15]. This study aimed to investigate epidemiological data to obtain outcomes of TB...

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Analysis of the immune response of human dendritic cells to Mycobacterium tuberculosis by quantitative proteomics

Cited by 9 publications

References 43 publications

Innate immunity in tuberculosis: host defense vs pathogen evasion

Innate immunity in tuberculosis: host defense vs pathogen evasion

Proteomics of Mycobacterium Infection: Moving towards a Better Understanding of Pathogen-Driven Immunomodulation

Fenofibrate Facilitates Post-Active Tuberculosis Infection in Macrophages and is Associated with Higher Mortality in Patients under Long-Term Treatment

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