scholarly journals Bacillus anthracis Capsule Activates Caspase-1 and Induces Interleukin-1β Release from Differentiated THP-1 and Human Monocyte-Derived Dendritic Cells

2009 ◽  
Vol 78 (1) ◽  
pp. 387-392 ◽  
Author(s):  
Min-Hee Cho ◽  
Hae-Jeong Ahn ◽  
Hyun-Joon Ha ◽  
Jungchan Park ◽  
Jeong-Hoon Chun ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Bacillus Anthracis ◽  
Innate Immune Response ◽  
Human Monocyte ◽  
Innate Immune ◽  
Interleukin 1Β ◽  
Dependent Manner ◽  
Caspase 1 ◽  
Extracellular Release

ABSTRACT The poly-γ-d-glutamic acid (PGA) capsule is one of the major virulence factors of Bacillus anthracis, which causes a highly lethal infection. The antiphagocytic PGA capsule disguises the bacilli from immune surveillance and allows unimpeded growth of bacilli in the host. Recently, efforts have been made to include PGA as a component of anthrax vaccine; however, the innate immune response of PGA itself has been poorly investigated. In this study, we characterized the innate immune response elicited by PGA in the human monocytic cell line THP-1, which was differentiated into macrophages with phorbol 12-myristate 13-acetate (PMA) and human monocyte-derived dendritic cells (hMoDCs). PGA capsules were isolated from the culture supernatant of either the pXO1-cured strain of B. anthracis H9401 or B. licheniformis ATCC 9945a. PGA treatment of differentiated THP-1 cells and hMoDCs led to the specific extracellular release of interleukin-1β (IL-1β) in a dose-dependent manner. Evaluation of IL-1β processing by Western blotting revealed that cleaved IL-1β increased in THP-1 cells and hMoDCs after PGA treatment. Enhanced processing of IL-1β directly correlated with increased activation of its upstream regulator, caspase-1, also known as IL-1β-converting enzyme (ICE). The extracellular release of IL-1β in response to PGA was ICE dependent, since the administration of an ICE inhibitor prior to PGA treatment blocked induction of IL-1β. These results demonstrate that B. anthracis PGA elicits IL-1β production through activation of ICE in PMA-differentiated THP-1 cells and hMoDCs, suggesting the potential for PGA as a therapeutic target for anthrax.

Differential modulation of innate immune response by epinephrine and estradiol

2017 ◽  
Vol 30 (3) ◽  
Author(s):  
Sona Margaryan ◽  
Armenuhi Hyusyan ◽  
Anush Martirosyan ◽  
Shushan Sargsian ◽  
Gayane Manukyan
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Dependent Manner ◽  
Induced Expression ◽  
Short Term Exposure ◽  
Tnf Α ◽  
Vitro Effect ◽  
Dose Dependent

AbstractBackgroundAlthough it is widely accepted that catecholamines and estrogens influence immunity and have consequences for health, their effect on innate immunity (e.g. monocytes and neutrophils) is still not fully investigated.Materials and methodsOur study aimed to analyze the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1 and IL-8 by whole blood cells following short-term exposure to epinephrine (Epi) and 17β-estradiol (E2) in the presence or absence of lipopolysaccharide (LPS). We also evaluated the in vitro effect of these hormones on expression of β2 integrin (CD11b/CD18) and L-selectin (CD62L) by circulating neutrophils and monocytes in the blood of healthy subjects.ResultsEpi has shown a potential to modulate the production of pro-inflammatory mediators. Its exposure resulted in significantly increased production of IL-8 in a dose-dependent manner. On the contrary, a dose-dependent suppression of LPS-induced production of IL-1β, IL-8, and MCP-1 by Epi was observed. In neutrophils, a modest rise in CD11b expression was observed after Epi exposure. Simultaneously, Epi suppressed LPS-induced expression of CD11b and CD18. In monocytes, Epi suppressed LPS-induced expression of C11b. E2 inhibited LPS-induced TNF-α production and caused a significant decrease in CD62L expression in both cell populations. No significant changes were observed after double exposure of cells with Epi and E2.ConclusionsThus, our results show that Epi and E2 differentially modulate the innate immune response and have a dual effect on cytokine modulation. The findings suggest that the observed immunoregulatory role of Epi and E2 may influence the outcome in endotoxin responses and can be critical in the regulation of inflammatory responses.

scholarly journals Salmonella escapes adaptive immune response via SIRT2 mediated modulation of innate immune response in dendritic cells

2018 ◽  
Vol 14 (11) ◽  
pp. e1007437 ◽  
Author(s):  
Mayuri Gogoi ◽  
Kasturi Chandra ◽  
Mohsen Sarikhani ◽  
Ramya Ramani ◽  
Nagalingam Ravi Sundaresan ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Innate Immune Response ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Adaptive Immune

scholarly journals The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression

Oncogene ◽  
2020 ◽  
Vol 39 (44) ◽  
pp. 6841-6855 ◽  
Author(s):  
Christina Jessen ◽  
Julia K. C. Kreß ◽  
Apoorva Baluapuri ◽  
Anita Hufnagel ◽  
Werner Schmitz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Transcription Factor ◽  
Prostaglandin E2 ◽  
Innate Immune Response ◽  
Stress Responses ◽  
Melanoma Cells ◽  
Innate Immune ◽  
Dependent Manner

AbstractThe transcription factor NRF2 is the major mediator of oxidative stress responses and is closely connected to therapy resistance in tumors harboring activating mutations in the NRF2 pathway. In melanoma, such mutations are rare, and it is unclear to what extent melanomas rely on NRF2. Here we show that NRF2 suppresses the activity of the melanocyte lineage marker MITF in melanoma, thereby reducing the expression of pigmentation markers. Intriguingly, we furthermore identified NRF2 as key regulator of immune-modulating genes, linking oxidative stress with the induction of cyclooxygenase 2 (COX2) in an ATF4-dependent manner. COX2 is critical for the secretion of prostaglandin E2 and was strongly induced by H2O2 or TNFα only in presence of NRF2. Induction of MITF and depletion of COX2 and PGE2 were also observed in NRF2-deleted melanoma cells in vivo. Furthermore, genes corresponding to the innate immune response such as RSAD2 and IFIH1 were strongly elevated in absence of NRF2 and coincided with immune evasion parameters in human melanoma datasets. Even in vitro, NRF2 activation or prostaglandin E2 supplementation blunted the induction of the innate immune response in melanoma cells. Transcriptome analyses from lung adenocarcinomas indicate that the observed link between NRF2 and the innate immune response is not restricted to melanoma.

scholarly journals TRAF6 and TAK1 contribute to SAMHD1-mediated negative regulation of NF-κB signaling

2020 ◽  
Author(s):  
Constanza E. Espada ◽  
Corine St. Gelais ◽  
Serena Bonifati ◽  
Victoria V. Maksimova ◽  
Michael P. Cahill ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Transforming Growth Factor ◽  
Negative Regulation ◽  
Innate Immune ◽  
Negative Regulator ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Intracellular Dntp ◽  
Hiv 1

Sterile alpha motif and HD-domain-containing protein 1 (SAMHD1) restricts HIV-1 replication by limiting the intracellular dNTP pool. SAMHD1 also suppresses the activation of NF-κB in response to viral infections and inflammatory stimuli. However, the mechanisms by which SAMHD1 negatively regulates this pathway remain unclear. Here we show that SAMHD1-mediated suppression of NF-κB activation is modulated by two key mediators of NF-κB signaling, tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and transforming growth factor-ß-activated kinase-1 (TAK1). We compared NF-κB activation stimulated by interleukin (IL)-1ß in monocytic THP-1 control and SAMHD1 knockout (KO) cells with and without partial TRAF6 knockdown (KD), or in cells treated with TAK1 inhibitors. Relative to control cells, IL-1ß-treated SAMHD1 KO cells showed increased phosphorylation of the inhibitor of NF-κB (IκBα), an indication of pathway activation, and elevated levels of TNF-α mRNA. Moreover, SAMHD1 KO combined with TRAF6 KD or pharmacological TAK1 inhibition reduced IκBα phosphorylation and TNF-α mRNA to the level of control cells. SAMHD1 KO cells infected with single-cycle HIV-1 showed elevated infection and TNF-α mRNA levels compared to control cells, and the effects were significantly reduced by TRAF6 KD or TAK1 inhibition. We further demonstrated that overexpressed SAMHD1 inhibited TRAF6-stimulated NF-κB reporter activity in HEK293T cells in a dose-dependent manner. SAMHD1 contains a nuclear localization signal (NLS), but an NLS-defective SAMHD1 exhibited a suppressive effect similar to the wild-type protein. Our data suggest that the TRAF6-TAK1 axis contributes to SAMHD1-mediated suppression of NF-κB activation and HIV-1 infection. Importance Cells respond to pathogen infection by activating a complex innate immune signaling pathway, which culminates in the activation of transcription factors and secretion of a family of functionally and genetically related cytokines. However, excessive immune activation may cause tissue damage and detrimental effects on the host. Therefore, in order to maintain host homeostasis, the innate immune response is tightly regulated during viral infection. We have reported SAMHD1 as a novel negative regulator of the innate immune response. Here, we provide new insights into SAMHD1-mediated negative regulation of the NF-κB pathway at the TRAF6-TAK1 checkpoint. We show that SAMHD1 inhibits TAK1 activation and TRAF6 signaling in response to proinflammatory stimuli. Interestingly, TRAF6 knockdown in SAMHD1-deficient cells significantly inhibited HIV-1 infection and activation of NF-κB induced by virus infection. Our research reveals a new negative regulatory mechanism by which SAMHD1 participates in the maintenance of cellular homeostasis during HIV-1 infection and inflammation.

scholarly journals Comparison of Two Mice Strains, A/J and C57BL/6, in Caspase-1 Activity and IL-1βSecretion of Macrophage toMycobacterium lepraeInfection

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Tae Jin Kang ◽  
Geum Seon Lee ◽  
Se Kon Kim ◽  
Song Hou Jin ◽  
Gue Tae Chae
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Mycobacterium Leprae ◽  
Adaptor Proteins ◽  
Innate Immune ◽  
Intracellular Pathogens ◽  
Caspase 1 ◽  
Molecular Patterns

A/J mice were found to have amino acid differences in Naip5, one of the NOD-like receptors (NLRs) involved in the cytosolic recognition of pathogen-associated molecular patterns and one of the adaptor proteins for caspase-1 activation. This defect was associated with a susceptibility toLegionellainfection, suggesting an important role for Naip5 in the immune response also to other intracellular pathogens, such asMycobacterium leprae. In this study, the immune responses of macrophages from A/J mice againstM. lepraewere compared to those of macrophages from C57BL/6 mice. Infection withM. lepraeinduced high levels of TNF-αproduction and NF-κB activation in A/J and C57BL/6 macrophages. Caspase-1 activation and IL-1βsecretion were also induced in both macrophages. However, macrophages from A/J mice exhibited reduced caspase-1 activation and IL-1βsecretion compared to C57BL/6 macrophages. These results suggest that NLR family proteins may have a role in the innate immune response toM. leprae.

scholarly journals ER stress and its regulator X-box-binding protein-1 enhance polyIC-induced innate immune response in dendritic cells

2011 ◽  
Vol 41 (4) ◽  
pp. 1086-1097 ◽  
Author(s):  
Fanlei Hu ◽  
Xiaofei Yu ◽  
Hongxia Wang ◽  
Daming Zuo ◽  
Chunqing Guo ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Er Stress ◽  
Innate Immune Response ◽  
Binding Protein ◽  
Innate Immune

scholarly journals IL-18 Levels and the Outcome of Innate Immune Response to Lipopolysaccharide: Importance of a Positive Feedback Loop with Caspase-1 in IL-18 Expression

2002 ◽  
Vol 169 (5) ◽  
pp. 2536-2544 ◽  
Author(s):  
Vishwas D. Joshi ◽  
Dhananjaya V. Kalvakolanu ◽  
Jeffrey D. Hasday ◽  
Richard J. Hebel ◽  
Alan S. Cross
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Innate Immune ◽  
Positive Feedback Loop ◽  
Caspase 1

Vibrio parahaemolyticus Flagellin Stimulates the Maturation of Human Monocyte-Derived Dendritic Cells and Elicits Th1-Type Immune Response.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3872-3872
Author(s):  
Hyun-Kyu Kang ◽  
Myong-Suk Park ◽  
Shee-Eun Lee ◽  
Joon-Haeng Rhee ◽  
Jung-Sun Park ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Vibrio Parahaemolyticus ◽  
Human Monocyte ◽  
Phenotypic Change ◽  
Target Cells ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Functional Maturation

Abstract Flagellin, the principal component of bacterial flagella, interacts with Toll-like receptor (TLR5) and induces the generation of a pro-inflammation response and activation of host dendritic cells (DCs) in vivo. In this study, we investigated the role of Vibrio parahaemolyticus (V. parahaemolyticus)-derived flagellin as a DC maturation-inducing molecule. V. parahemolyticus-derived flagellin (100–1,000 ng/ml) induced the maturation of human monocyte-derived dendritic cells in a concentration-dependent manner with maximal effect at 500 ng/ml of flagellin as determined by increased levels of surface markers, namely, CD1a, CD80, CD86, CD83, and HLA-DR, a response which could be compared with the phenotypic change in immature DCs (iDCs) treated with lipopolysaccharide (LPS) or cytokine cocktails (CC) with TNF-α, IL-1β, IL-6, and PGE2. Moreover, V. parahaemolyticus-derived flagellin also reduced phagocytic activity, and increased IL-12 production in a polymyxin B-insensitive manner and DC-mediated T cell proliferation, which is comparable with that of LPS- or CC-treated iDCs at several responder to stimulator ratios, suggesting the functional maturation of DCs by V. parahaemolyticus-derived flagellin. Maturation of DCs by V. parahaemolyticus-derived flagellin also elicited a significant increase in specific cytotoxic activity against target cells at several effector to target cells ratios as determined by 51Cr-release assay, and induced Th1-type immune response, such as increase in INF-γ producing cells, determined by ELISPOT assay and analysis of intracellular cytokine staining assay. Taken together, this study demonstrates the role of V. parahaemolyticus-derived flagellin in the functional maturation of DCs, and suggests that V. parahaemolyticus-derived flagellin as a useful molecule for the development of a DC-based immunotherapy against tumors.

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