Impaired Generation of Reactive Oxygen Species during Differentiation of Dendritic Cells (DCs) by<i>Mycobacterium tuberculosis</i>Secretory Antigen (MTSA) and Subsequent Activation of MTSA-DCs by Mycobacteria Results in Increased Intracellular Survival

Sinha, Aprajita; Singh, Amit Kumar; Satchidanandam, Vijaya; Natarajan, Krishnamurthy

doi:10.4049/jimmunol.177.1.468

Cited by 49 publications

(61 citation statements)

References 68 publications

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“…The ability of hematopoietic growth factors to induce ROS is critical to drive cell proliferation (9,16,34). HPCs produce a small increase of ROS, peaking at 30 min after GM-CSF stimulation (9). In line with the previous finding, using CM-H 2 DCFDA, we detected a low level of ROS, which provides support for initial rapid HPC division and moderate DC generation in the first 4 d of culture.…”

Section: Discussionsupporting

confidence: 76%

“…1C). The ability of hematopoietic growth factors to induce ROS is critical to drive cell proliferation (9,16,34). HPCs produce a small increase of ROS, peaking at 30 min after GM-CSF stimulation (9).…”

Section: Discussionmentioning

confidence: 99%

“…1A, 1B). GM-CSF was shown to induce a low level of ROS in HPCs (8,9). We next measured ROS during DC generation by the probe CM-H 2 DCFDA.…”

Section: The Level Of Ros Soars When DC Expansion Is Rapidmentioning

confidence: 99%

“…Hematopoietic growth factors such as GM-CSF for DC induction have been shown to signal through formation of reactive oxygen species (ROS) (8,9). ROS represent a group of molecular entities that are either free radicals containing unpaired electrons, such as superoxide, NO, and hydroxyl radical, or nonradical oxidizing agents, such as H 2 O 2 and the NO derivative peroxynitrite (10).…”

mentioning

confidence: 99%

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Reactive Oxygen Species Level Defines Two Functionally Distinctive Stages of Inflammatory Dendritic Cell Development from Mouse Bone Marrow

Sheng

Pietersz²,

Tang³

et al. 2010

The Journal of Immunology

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Reactive oxygen species (ROS) have been implicated in various physiological activities. However, their role in dendritic cell (DC) activation and generation has not been investigated. Using the bone marrow-derived GM-CSF–induced ex vivo DC model, we characterize how induction of ROS correlates with inflammatory DC functionality and expansion. We describe that the functionality of GM-CSF–induced DCs is distinct in two developmental stages. Whereas division of DC-committed hematopoietic progenitor cells (HPCs) neared completion by day 6, the level of ROS soared after day 4. Day 3 ROSlo DCs were highly responsive to TLR stimuli such as LPS and zymosan by rapid upregulation of CD80, CD86, and MHC class II, in contrast to the low response of day 6 ROShi DCs. ROShi DCs could not initiate and sustain a significant level of NF-κB phosphorylation in response to LPS and zymosan, although demonstrating hyperactivation of p38 MAPK by LPS, in a fashion disparate to ROSlo DCs. ROSlo DCs stimulated a higher level of allogeneic and OVA-specific T cell proliferative responses, although ROShi DCs were much more proficient in processing OVA. In response to pathogenic stimuli, ROShi DCs also demonstrated rapid cellular adhesion and H2O2 release, indicating their role in immediate microbial targeting. Moreover, HPC expansion and DC generation were dependent on the surge of ROS in an NADPH oxidase-independent manner. These findings point to the potential role of cellular ROS in mediating functionality and development of DCs from HPCs during inflammation.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

“…1A, 1B). GM-CSF was shown to induce a low level of ROS in HPCs (8,9). We next measured ROS during DC generation by the probe CM-H 2 DCFDA.…”

Section: The Level Of Ros Soars When DC Expansion Is Rapidmentioning

confidence: 99%

mentioning

confidence: 99%

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Reactive Oxygen Species Level Defines Two Functionally Distinctive Stages of Inflammatory Dendritic Cell Development from Mouse Bone Marrow

Sheng

Pietersz²,

Tang³

et al. 2010

The Journal of Immunology

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“…GM-CSF has been reported to cause a rapid increase in ROS production in several cell lines [11,27,28]. Thus, experiments were carried out to ascertain whether GM-CSF increased ROS generation in monocytes.…”

Section: Analysis Of Gm-csf-induced Ros Productionmentioning

confidence: 99%

Role of mitochondria and reactive oxygen species in dendritic cell differentiation and functions

Prete

Zaccagnino

Paola

et al. 2008

Free Radical Biology and Medicine

100

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Dendritic cells (DC) are potent antigen-presenting cells capable of inducing T and B responses and immune tolerance. We have characterized some aspects of energy metabolism accompanying the differentiation process of human monocytes into DC. Compared to precursor monocytes, DC exhibited a much larger number of mitochondria and consistently (i) a higher endogenous respiratory activity and (ii) a more than sixfold increase in ATP content and an even larger increase in the activity of the mitochondrial marker enzyme citrate synthase. The presence in the culture medium of rotenone, an inhibitor of the respiratory chain Complex I, prevented the increase in mitochondrial number and ATP level, without affecting cell viability. Rotenone inhibited DC differentiation, as revealed by the observation that the expression of CD1a, which is a specific surface marker of DC differentiation, was strongly reduced. Cells cultured in the presence of rotenone displayed a lower content of growth factor-induced, mitochondrially generated, hydrogen peroxide. A similar drop in ROS was observed upon addition of catalase, which caused functional effects similar to those produced by rotenone treatment. These results suggest that ROS play a crucial role in DC differentiation and that mitochondria are an important source of ROS in this process. © 2008 Elsevier Inc. All rights reserved.Keywords: Dendritic cells; Mitochondria; Reactive oxygen species; Oxidative phosphorylation; Free radicals Effective immune responses require correct localization and functioning of dendritic cells (DC). Dendritic cells are the most potent and versatile antigen-presenting cells, with a unique ability to induce specific immune responses as well as tolerance [1,2]. In peripheral tissues they reside in an immature state waiting for incoming antigens. After capturing and processing the antigens, DC undergo a maturation process which culminates in dramatic changes in functions and migratory properties [3,4]. The localization of mature DC to the draining lymph nodes coincides with the presentation of processed antigens to naïve T cells, triggering the initiation of specific immune responses [2,5]. An in vitro method to differentiate immature DC from CD14 + monocyte precursors cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) is very well established [6,7].Reactive oxygen species (ROS) have been identified as important second messengers involved in the transduction of several signaling pathways [8,9], gene expression, and cell proliferation [10]. Furthermore, recent studies have shown that growth factors, through the actions of their specific receptors, are able to increase

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Mycobacterium tuberculosis: immune response, biomarkers, and therapeutic intervention

Zhuang,

Yang,

et al. 2024

MedComm

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Although tuberculosis (TB) is an infectious disease, the progression of the disease following Mycobacterium tuberculosis (MTB) infection is closely associated with the host's immune response. In this review, a comprehensive analysis of TB prevention, diagnosis, and treatment was conducted from an immunological perspective. First, we delved into the host's immune response mechanisms against MTB infection as well as the immune evasion mechanisms of the bacteria. Addressing the challenges currently faced in TB diagnosis and treatment, we also emphasized the importance of protein, genetic, and immunological biomarkers, aiming to provide new insights for early and personalized diagnosis and treatment of TB. Building upon this foundation, we further discussed intervention strategies involving chemical and immunological treatments for the increasingly critical issue of drug‐resistant TB and other forms of TB. Finally, we summarized TB prevention, diagnosis, and treatment challenges and put forward future perspectives. Overall, these findings provide valuable insights into the immunological aspects of TB and offer new directions toward achieving the WHO's goal of eradicating TB by 2035.

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Impaired Generation of Reactive Oxygen Species during Differentiation of Dendritic Cells (DCs) byMycobacterium tuberculosisSecretory Antigen (MTSA) and Subsequent Activation of MTSA-DCs by Mycobacteria Results in Increased Intracellular Survival

Cited by 49 publications

References 68 publications

Reactive Oxygen Species Level Defines Two Functionally Distinctive Stages of Inflammatory Dendritic Cell Development from Mouse Bone Marrow

Reactive Oxygen Species Level Defines Two Functionally Distinctive Stages of Inflammatory Dendritic Cell Development from Mouse Bone Marrow

Role of mitochondria and reactive oxygen species in dendritic cell differentiation and functions

Mycobacterium tuberculosis: immune response, biomarkers, and therapeutic intervention

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