Paclitaxel Enhances the Innate Immunity by Promoting NLRP3 Inflammasome Activation in Macrophages.

Abstract:

:Microtubules play critical roles in regulating the activation of NLRP3 inflammasome and microtubule-destabilizing agents such as colchicine have been shown to suppress the activation of this inflammasome. However, it remains largely unknown whether paclitaxel, a microtubule-stabilizing agent being used in cancer therapy, has any influences on NLRP3 inflammasome activation. Here we showed that paclitaxel pre-treatment greatly enhanced ATP- or nigericin-induced NLRP3 inflammasome activation as indicated by increased release of cleaved caspase-1 and mature IL-1β, enhanced formation of ASC speck, and increased gasdermin D cleavage and pyroptosis. Paclitaxel time- and dose-dependently induced α-tubulin acetylation in LPS-primed murine and human macrophages and further increased ATP- or nigericin-induced α-tubulin acetylation. Such increased α-tubulin acetylation was significantly suppressed either by resveratrol or NAD+ (coenzyme required for deacetylase activity of SIRT2), or by genetic knockdown of MEC-17 (gene encoding α-tubulin acetyltransferase 1). Concurrently, the paclitaxel-mediated enhancement of NLRP3 inflammasome activation was significantly suppressed by resveratrol, NAD+, or MEC-17 knockdown, indicating the involvement of paclitaxel-induced α-tubulin acetylation in the augmentation of NLRP3 inflammasome activation. Similar to paclitaxel, epothilone B that is another microtubule-stabilizing agent also induced α-tubulin acetylation and increased NLRP3 inflammasome activation in macrophages in response to ATP treatment. Consistent with the in vitro results, intraperitoneal administration of paclitaxel significantly increased serum IL-1β levels, reduced bacterial burden, dampened infiltration of inflammatory cells in the liver, and improved animal survival in a mouse model of bacterial infection. Collectively, our data indicate that paclitaxel potentiated NLRP3 inflammasome activation by inducing α-tubulin acetylation and thereby conferred enhanced antibacterial innate responses, suggesting its potential application against pathogenic infections beyond its use as a chemotherapeutic agent.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Zeng QZ,Yang F,Li CG,Xu LH,He XH,Mai FY,Zeng CY,Zhang CC,Zha QB,Ouyang DY

doi

10.3389/fimmu.2019.00072

subject

Has Abstract

pub_date

2019-01-29 00:00:00

pages

72

issn

1664-3224

journal_volume

10

pub_type

杂志文章
  • Autologous Hematopoietic Stem Cell Transplantation for Treatment of Systemic Sclerosis.

    abstract::Systemic Sclerosis (SSc) is a complex autoimmune disease, characterized by high mortality and morbidity. The heterogeneity in terms of extent, severity, and rate of progression of skin and internal organ involvement gives rise to many difficulties in finding the optimal therapeutic interventions for SSc and, to date, ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.02390

    authors: Del Papa N,Pignataro F,Zaccara E,Maglione W,Minniti A

    更新日期:2018-10-16 00:00:00

  • Inducers, Attractors and Modulators of CD4+ Treg Cells in Non-Small-Cell Lung Cancer.

    abstract::Lung cancer is the leading cause of cancer-associated deaths worldwide, with non-small cell-lung cancer (NSCLC) accounting for approximately 80% of cases. Immune escape has been demonstrated to play a key role in the initiation and progression of NSCLC, although the underlying mechanisms are diverse and their puzzling...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.00676

    authors: Xie M,Wei J,Xu J

    更新日期:2020-04-28 00:00:00

  • Monocytic Myeloid-Derived Suppressor Cells in Chronic Infections.

    abstract::Heterogeneous populations of myeloid regulatory cells (MRC), including monocytes, macrophages, dendritic cells, and neutrophils, are found in cancer and infectious diseases. The inflammatory environment in solid tumors as well as infectious foci with persistent pathogens promotes the development and recruitment of MRC...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.01895

    authors: Dorhoi A,Du Plessis N

    更新日期:2018-01-04 00:00:00

  • Distinguishing Sepsis From Infection by Neutrophil Dysfunction: A Promising Role of CXCR2 Surface Level.

    abstract::Sepsis is one of the well-established diseases with specific patterns of neutrophil dysfunctions. Previous studies demonstrated sepsis-related neutrophil dysfunctions in comparison with subjects without infection. Since sepsis and infection are recently recognized as distinctive processes, whether these neutrophil dys...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.608696

    authors: Seree-Aphinan C,Vichitkunakorn P,Navakanitworakul R,Khwannimit B

    更新日期:2020-12-23 00:00:00

  • CD4 T Cell Determinants in West Nile Virus Disease and Asymptomatic Infection.

    abstract::West Nile (WN) virus infection of humans is frequently asymptomatic, but can also lead to WN fever or neuroinvasive disease. CD4 T cells and B cells are critical in the defense against WN virus, and neutralizing antibodies, which are directed against the viral glycoprotein E, are an accepted correlate of protection. F...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00016

    authors: Koblischke M,Spitzer FS,Florian DM,Aberle SW,Malafa S,Fae I,Cassaniti I,Jungbauer C,Knapp B,Laferl H,Fischer G,Baldanti F,Stiasny K,Heinz FX,Aberle JH

    更新日期:2020-01-23 00:00:00

  • Allogeneic HSCT for Autoimmune Diseases: A Retrospective Study From the EBMT ADWP, IEWP, and PDWP Working Parties.

    abstract::Background: This retrospective study assessed the use and long-term outcome of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with severe autoimmune diseases (ADs), reported to the European Society for Blood and Marrow Transplantation (EBMT) registry. Methods: Between 1997 and 2014, 128 patients...

    journal_title:Frontiers in immunology

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.3389/fimmu.2019.01570

    authors: Greco R,Labopin M,Badoglio M,Veys P,Furtado Silva JM,Abinun M,Gualandi F,Bornhauser M,Ciceri F,Saccardi R,Lankester A,Alexander T,Gennery AR,Bader P,Farge D,Snowden JA

    更新日期:2019-07-04 00:00:00

  • Protective Effects of Aryl Hydrocarbon Receptor Signaling in Celiac Disease Mucosa and in Poly I:C-Induced Small Intestinal Atrophy Mouse Model.

    abstract::Aryl hydrocarbon receptor (AhR), a transcription factor activated by a large number of natural and synthetic agents, modulates the activity of immune cells in the gut and represents an important link between the environment and immune-mediated pathologies. In this study, we investigated the role of AhR in celiac disea...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00091

    authors: Dinallo V,Marafini I,Di Fusco D,Di Grazia A,Laudisi F,Dwairi R,Paoluzi OA,Monteleone G,Monteleone I

    更新日期:2019-02-04 00:00:00

  • IL-23 Contributes to Campylobacter jejuni-Induced Intestinal Pathology via Promoting IL-17 and IFNγ Responses by Innate Lymphoid Cells.

    abstract::Human pathogen Campylobacter jejuni is a significant risk factor for the development of long-term intestinal dysfunction although the cellular and molecular mechanisms remain scantily defined. IL-23 is an emerging therapeutic target for the treatment of inflammatory intestinal diseases, however its role in C. jejuni-d...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.579615

    authors: Jing X,Korchagina AA,Shein SA,Muraoka WT,Koroleva E,Tumanov AV

    更新日期:2021-01-06 00:00:00

  • IRF-7 Mediates Type I IFN Responses in Endotoxin-Challenged Mice.

    abstract::IRF-7 mediates robust production of type I IFN via MyD88 of the TLR9 pathway in plasmacytoid dendritic cells (pDCs). Previous in vitro studies using bone marrow-derived dendritic cells lacking either Irf7 or Irf3 have demonstrated that only IRF-3 is required for IFN-β production in the TLR4 pathway. Here, we show that...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00640

    authors: Sin WX,Yeong JP,Lim TJF,Su IH,Connolly JE,Chin KC

    更新日期:2020-04-16 00:00:00

  • Evaluation of Alpha-1 Antitrypsin Levels and SERPINA1 Gene Polymorphisms in Sickle Cell Disease.

    abstract::Alpha-1 antitrypsin (AAT) is an inhibitor of neutrophil elastase and a member of the serine proteinase inhibitor (serpin) superfamily, and little is known about its activity in sickle cell disease (SCD). We hypothesize that AAT may undergo changes in SCD because of the high oxidative stress and inflammation associated...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01491

    authors: Carvalho MOS,Souza ALCS,Carvalho MB,Pacheco APAS,Rocha LC,do Nascimento VML,Figueiredo CVB,Guarda CC,Santiago RP,Adekile A,Goncalves MS

    更新日期:2017-11-06 00:00:00

  • NLRC5 Functions beyond MHC I Regulation-What Do We Know So Far?

    abstract::NLRC5 is a member of the NLR family that acts as a transcriptional activator of MHC class I genes. In line with the function of several related NLR proteins in innate immune responses, there is, however, also ample evidence that NLRC5 contributes to innate and adaptive immune responses beyond the regulation of MHC cla...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00150

    authors: Benkő S,Kovács EG,Hezel F,Kufer TA

    更新日期:2017-02-17 00:00:00

  • Developmental and Functional Control of Natural Killer Cells by Cytokines.

    abstract::Natural killer (NK) cells are effective in combating infections and tumors and as such are tempting for adoptive transfer therapy. However, they are not homogeneous but can be divided into three main subsets, including cytotoxic, tolerant, and regulatory NK cells, with disparate phenotypes and functions in diverse tis...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00930

    authors: Wu Y,Tian Z,Wei H

    更新日期:2017-08-04 00:00:00

  • S100A12 Expression Is Modulated During Monocyte Differentiation and Reflects Periodontitis Severity.

    abstract::S100A12 is a calcium-binding protein of the S100 subfamily of myeloid-related proteins that acts as an alarmin to induce a pro-inflammatory innate immune response. It has been linked to several chronic inflammatory diseases, however its role in the common oral immunopathology periodontitis is largely unknown. Previous...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00086

    authors: Lira-Junior R,Holmström SB,Clark R,Zwicker S,Majster M,Johannsen G,Axtelius B,Åkerman S,Svensson M,Klinge B,Boström EA

    更新日期:2020-01-31 00:00:00

  • Low-Dose Total Body Irradiation Can Enhance Systemic Immune Related Response Induced by Hypo-Fractionated Radiation.

    abstract::A systemic immune related response (SIME) of radiotherapy has been occasionally observed on metastatic tumors, but the clinical outcomes remain poor. Novel treatment approaches are therefore needed to improve SIME ratio. We used a combination of hypo-fractionated radiation therapy (H-RT) with low-dose total body irrad...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00317

    authors: Liu J,Zhou J,Wu M,Hu C,Yang J,Li D,Wu P,Chen Y,Chen P,Lin S,Cui Y,Fu S,Wu J

    更新日期:2019-02-27 00:00:00

  • Novel, Anti-hTNF-α Variable New Antigen Receptor Formats with Enhanced Neutralizing Potency and Multifunctionality, Generated for Therapeutic Development.

    abstract::The management of chronic inflammatory diseases, such as inflammatory bowel disease, psoriasis, and rheumatoid arthritis has significantly improved over the last decade with the clinical availability of anti-TNF-α biologics. Despite this undoubted treatment success, a combination of acquired resistance together with a...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01780

    authors: Ubah OC,Steven J,Kovaleva M,Ferguson L,Barelle C,Porter AJR,Barelle CJ

    更新日期:2017-12-22 00:00:00

  • The Contribution of CD40/CD40L Axis in Inflammatory Bowel Disease: An Update.

    abstract::Inflammatory bowel disease (IBD) is a chronic and multifactorial disease of the gastrointestinal tract. The exact etiology of IBD remains complex and unclear involving an inadequately defined relationship between microbial insult, genetic predisposition, altered intestinal barrier permeability, oxidative stress compon...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2015.00529

    authors: Senhaji N,Kojok K,Darif Y,Fadainia C,Zaid Y

    更新日期:2015-10-16 00:00:00

  • Novel Chimeric Protein Vaccines Against Clostridium difficile Infection.

    abstract::Clostridium difficile infection (CDI) is the leading cause of world-wide nosocomial acquired diarrhea in adults. Active vaccination is generally accepted as a logical and cost-effective approach to prevent CDI. In this paper, we have generated two novel chimeric proteins; one designated Tcd169, comprised of the glucos...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02440

    authors: Wang S,Wang Y,Cai Y,Kelly CP,Sun X

    更新日期:2018-10-22 00:00:00

  • Mast Cell Coupling to the Kallikrein-Kinin System Fuels Intracardiac Parasitism and Worsens Heart Pathology in Experimental Chagas Disease.

    abstract::During the course of Chagas disease, infectious forms of Trypanosoma cruzi are occasionally liberated from parasitized heart cells. Studies performed with tissue culture trypomastigotes (TCTs, Dm28c strain) demonstrated that these parasites evoke neutrophil/CXCR2-dependent microvascular leakage by activating innate se...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00840

    authors: Nascimento CR,Andrade D,Carvalho-Pinto CE,Serra RR,Vellasco L,Brasil G,Ramos-Junior ES,da Mota JB,Almeida LN,Andrade MV,Correia Soeiro MN,Juliano L,Alvarenga PH,Oliveira AC,Sicuro FL,de Carvalho ACC,Svensjö E,Scharfstei

    更新日期:2017-08-02 00:00:00

  • A Novel Role for Triglyceride Metabolism in Foxp3 Expression.

    abstract::Lipid metabolism plays a key role in many cellular processes. We show here that regulatory T cells have enhanced lipid storage within subcellular lipid droplets (LD). They also express elevated amounts of both isoforms of diacylglycerol acyl transferase (DGAT1 & 2), enzymes required for the terminal step of triacylgly...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01860

    authors: Howie D,Ten Bokum A,Cobbold SP,Yu Z,Kessler BM,Waldmann H

    更新日期:2019-08-13 00:00:00

  • Neutrophil Extracellular Traps Promote Inflammatory Responses in Psoriasis via Activating Epidermal TLR4/IL-36R Crosstalk.

    abstract::Epidermal infiltration of neutrophils is a hallmark of psoriasis, where their activation leads to release of neutrophil extracellular traps (NETs). The contribution of NETs to psoriasis pathogenesis has been unclear, but here we demonstrate that NETs drive inflammatory responses in skin through activation of epidermal...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00746

    authors: Shao S,Fang H,Dang E,Xue K,Zhang J,Li B,Qiao H,Cao T,Zhuang Y,Shen S,Zhang T,Qiao P,Li C,Gudjonsson JE,Wang G

    更新日期:2019-04-05 00:00:00

  • A Higher Abundance of O-Linked Glycans Confers a Selective Advantage to High Fertile Buffalo Spermatozoa for Immune-Evasion From Neutrophils.

    abstract::The glycans on the plasma membrane of cells manifest as the glycocalyx, which serves as an information-rich frontier that is directly in contact with its immediate milieu. The glycoconjugates (GCs) that adorn most of the mammalian cells are also abundant in gametes, especially the spermatozoa where they perform unique...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01928

    authors: Batra V,Dagar K,Nayak S,Kumaresan A,Kumar R,Datta TK

    更新日期:2020-08-28 00:00:00

  • Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease.

    abstract::Background: Chagas cardiomyopathy is the main fibrosing myocarditis among known heart diseases. Development of cardiomyopathy has been related to extracellular matrix (ECM) remodeling, which are controlled by matrix metalloproteinases (MMPs) and cytokines, especially interleukin (IL)-1β. The convertion of 31KDa inacti...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00800

    authors: Medeiros NI,Pinto BF,Elói-Santos SM,Teixeira-Carvalho A,Magalhães LMD,Dutra WO,Correa-Oliveira R,Gomes JAS

    更新日期:2019-04-18 00:00:00

  • Ultrasensitive Quantification of Cytokine Proteins in Single Lymphocytes From Human Blood Following ex-vivo Stimulation.

    abstract::In this study we demonstrate the feasibility of direct, quantitative measurement of cytokine proteins in single human CD8 lymphocytes from fresh peripheral blood of healthy donors following a brief ex vivo stimulation. Cytokine-secreting cells were identified using cell surface "catch" reagents and single cell data we...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02462

    authors: Saxena A,Dagur PK,Desai A,McCoy JP Jr

    更新日期:2018-10-23 00:00:00

  • Large-Scale Generation of Human Allospecific Induced Tregs With Functional Stability for Use in Immunotherapy in Transplantation.

    abstract::Regulatory T cells play an important role in the control of autoimmune diseases and maintenance of tolerance. In the context of transplantation, regulatory T cells (Tregs) have been proposed as new therapeutic tools that may induce allospecific tolerance toward the graft, avoiding the side effects induced by generaliz...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.00375

    authors: Alvarez-Salazar EK,Cortés-Hernández A,Arteaga-Cruz S,Alberú-Gómez J,Soldevila G

    更新日期:2020-04-02 00:00:00

  • The Heterogeneity, Origins, and Impact of Migratory iILC2 Cells in Anti-helminth Immunity.

    abstract::Soil-transmitted helminths represent a major global health burden with infections and infection-related comorbidities causing significant reductions in the quality of life for individuals living in endemic areas. Repeated infections and chronic colonization by these large extracellular worms in mammals led to the evol...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.01594

    authors: Miller MM,Reinhardt RL

    更新日期:2020-07-23 00:00:00

  • Reference Grade Characterization of Polymorphisms in Full-Length HLA Class I and II Genes With Short-Read Sequencing on the ION PGM System and Long-Reads Generated by Single Molecule, Real-Time Sequencing on the PacBio Platform.

    abstract::Although NGS technologies fuel advances in high-throughput HLA genotyping methods for identification and classification of HLA genes to assist with precision medicine efforts in disease and transplantation, the efficiency of these methods are impeded by the absence of adequately-characterized high-frequency HLA allele...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02294

    authors: Suzuki S,Ranade S,Osaki K,Ito S,Shigenari A,Ohnuki Y,Oka A,Masuya A,Harting J,Baybayan P,Kitazume M,Sunaga J,Morishima S,Morishima Y,Inoko H,Kulski JK,Shiina T

    更新日期:2018-10-04 00:00:00

  • The Role of the Immunological Synapse in Differential Effects of APC Subsets in Alloimmunization to Fresh, Non-stored RBCs.

    abstract::Background: Each year, over 5 million red blood cell (RBC) transfusions are administered to patients in the USA. Despite the therapeutic benefits of RBC transfusions, there are associated risks. RBC-specific alloantibodies may form in response to antigenic differences between RBC donors and recipients; these alloantib...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02200

    authors: Richards AL,Sheldon K,Wu X,Gruber DR,Hudson KE

    更新日期:2018-10-05 00:00:00

  • Profiling of Canonical and Non-Traditional Cytokine Levels in Interferon-β-Treated Relapsing-Remitting-Multiple Sclerosis Patients.

    abstract:Background:Multiple sclerosis (MS) is a chronic, progressive autoimmune disease of the central nervous system in which inflammation plays a key role in the induction, development, and progression. Most of the MS patients present with relapsing-remitting (RR) form, characterized by flare-ups followed by periods of recov...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.01240

    authors: D'Angelo C,Reale M,Costantini E,Di Nicola M,Porfilio I,de Andrés C,Fernández-Paredes L,Sánchez-Ramón S,Pasquali L

    更新日期:2018-06-04 00:00:00

  • Sex Bias in Asthma Prevalence and Pathogenesis.

    abstract::Sex-related differences in asthma prevalence are well established and change through the reproductive phases of life. As children, boys have increased prevalence of asthma compared to girls. However, as adults, women have increased prevalence of asthma compared to men. Many factors, including genetics, environment, im...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.02997

    authors: Shah R,Newcomb DC

    更新日期:2018-12-18 00:00:00

  • PI3Kδ Inhibition Enhances the Antitumor Fitness of Adoptively Transferred CD8+ T Cells.

    abstract::Phosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells. Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 t...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01221

    authors: Bowers JS,Majchrzak K,Nelson MH,Aksoy BA,Wyatt MM,Smith AS,Bailey SR,Neal LR,Hammerbacher JE,Paulos CM

    更新日期:2017-09-29 00:00:00