The Role of GM-CSF in Chronic Infections

1996 ◽  
pp. 559-563
Author(s):  
Charlotte Nath ◽  
Joginder Nath ◽  
S. C. Gulati
Keyword(s):  
Chronic Infections ◽  
Gm Csf

scholarly journals The MarR-Type Regulator PA3458 Is Involved in Osmoadaptation Control in Pseudomonas aeruginosa

2021 ◽  
Vol 22 (8) ◽  
pp. 3982
Author(s):  
Karolina Kotecka ◽  
Adam Kawalek ◽  
Kamil Kobylecki ◽  
Aneta Agnieszka Bartosik
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Binding Sites ◽  
Transcriptional Profiling ◽  
Mrna Level ◽  
Transcriptional Regulators ◽  
Resistance Mechanisms ◽  
Chronic Infections ◽  
Environmental Signals ◽  
Regulatory Systems

Pseudomonas aeruginosa is a facultative human pathogen, causing acute and chronic infections that are especially dangerous for immunocompromised patients. The eradication of P. aeruginosa is difficult due to its intrinsic antibiotic resistance mechanisms, high adaptability, and genetic plasticity. The bacterium possesses multilevel regulatory systems engaging a huge repertoire of transcriptional regulators (TRs). Among these, the MarR family encompasses a number of proteins, mainly acting as repressors, which are involved in response to various environmental signals. In this work, we aimed to decipher the role of PA3458, a putative MarR-type TR from P. aeruginosa. Transcriptional profiling of P. aeruginosa PAO1161 overexpressing PA3458 showed changes in the mRNA level of 133 genes; among them, 100 were down-regulated, suggesting the repressor function of PA3458. Concomitantly, ChIP-seq analysis identified more than 300 PA3458 binding sites in P. aeruginosa. The PA3458 regulon encompasses genes involved in stress response, including the PA3459–PA3461 operon, which is divergent to PA3458. This operon encodes an asparagine synthase, a GNAT-family acetyltransferase, and a glutamyl aminopeptidase engaged in the production of N-acetylglutaminylglutamine amide (NAGGN), which is a potent bacterial osmoprotectant. We showed that PA3458-mediated control of PA3459–PA3461 expression is required for the adaptation of P. aeruginosa growth in high osmolarity. Overall, our data indicate that PA3458 plays a role in osmoadaptation control in P. aeruginosa.

scholarly journals Obesity-Induced Dysbiosis Exacerbates IFN-γ Production and Pulmonary Inflammation in the Mycobacterium tuberculosis Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1732
Author(s):  
Sandra Patricia Palma Albornoz ◽  
Thais Fernanda de Campos Fraga-Silva ◽  
Ana Flávia Gembre ◽  
Rômulo Silva de Oliveira ◽  
Fernanda Mesquita de Souza ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Gut Microbiota ◽  
Inflammatory Diseases ◽  
Pulmonary Inflammation ◽  
Host Susceptibility ◽  
Chronic Infections ◽  
Mycobacterium Tuberculosis Infection ◽  
Pulmonary Damage ◽  
Ifn Γ

The microbiota of the gut–lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4+IFN-γ+IL-17− cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut–lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology.

scholarly journals Immunomodulatory Activities of Carica papaya L. Leaf Juice in a Non-Lethal, Symptomatic Dengue Mouse Model

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 501
Author(s):  
Mohd Ridzuan Mohd Abd Razak ◽  
Nor Azrina Norahmad ◽  
Nur Hana Md Jelas ◽  
Adlin Afzan ◽  
Norazlan Mohmad Misnan ◽  
...  
Keyword(s):  
Mouse Model ◽  
Carica Papaya ◽  
Viral Rna ◽  
Action Mechanism ◽  
Dengue Virus Infection ◽  
Gm Csf ◽  
Intracellular Cytokines ◽  
Freeze Dried ◽  
Leaf Juice

The role of Carica papaya L. leaf juice in immune dysregulation caused by dengue virus infection remains unclear. This study aimed to investigate the immunomodulatory activities of the freeze-dried C. papaya leaf juice (FCPLJ) on AG129 mice infected with a clinical DENV-2 (DMOF015) isolate. The infected AG129 mice were orally treated with 500 and 1000 mg/kg/day of FCPLJ, for three days. Platelet, leukocyte, lymphocyte and neutrophil counts were microscopically determined. The level of plasma proinflammatory cytokines was measured by multiplex immunoassay. The levels of intracellular cytokines and viral RNA were determined by RT-qPCR technique. The results showed that the FCPLJ treatment increased the total white blood cell and neutrophil counts in the infected mice. The FCPLJ treatment decreased the level of GM-CSF, GRO-alpha, IL-1 beta, IL-6, MCP-1 and MIP-1 beta in the plasma of the infected mice. The intracellular IL-6 and viral RNA levels in the liver of infected mice were decreased by the FCPLJ treatment. In conclusion, this study supports the potential immunomodulatory role of the FCPLJ in a non-lethal, symptomatic dengue mouse model. Further studies on the action mechanism of the C. papaya leaf juice and its possible use as adjunctive dengue immunotherapy are warranted.

scholarly journals Aging diminishes the resistance of AO rats to EAE: putative role of enhanced generation of GM-CSF Expressing CD4+ T cells in aged rats

2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Zorica Stojić-Vukanić ◽  
Mirjana Nacka-Aleksić ◽  
Ivan Pilipović ◽  
Ivana Vujnović ◽  
Veljko Blagojević ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Aged Rats ◽  
Gm Csf ◽  
Putative Role

scholarly journals TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia

2012 ◽  
Vol 302 (5) ◽  
pp. L447-L454 ◽  
Author(s):  
Louis R. Standiford ◽  
Theodore J. Standiford ◽  
Michael J. Newstead ◽  
Xianying Zeng ◽  
Megan N. Ballinger ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bacterial Pneumonia ◽  
Lavage Fluid ◽  
Alveolar Epithelial Cells ◽  
Intratracheal Administration ◽  
Bacterial Colony ◽  
Gram Negative ◽  
Gm Csf

Toll-like receptors (TLRs) are required for protective host defense against bacterial pathogens. However, the role of TLRs in regulating lung injury during Gram-negative bacterial pneumonia has not been thoroughly investigated. In this study, experiments were performed to evaluate the role of TLR4 in pulmonary responses against Klebsiella pneumoniae (Kp). Compared with wild-type (WT) (Balb/c) mice, mice with defective TLR4 signaling (TLR4lps-d mice) had substantially higher lung bacterial colony-forming units after intratracheal challenge with Kp, which was associated with considerably greater lung permeability and lung cell death. Reduced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA and protein was noted in lungs and bronchoalveolar lavage fluid of TLR4 mutant mice postintratracheal Kp compared with WT mice, and primary alveolar epithelial cells (AEC) harvested from TLR4lps-d mice produced significantly less GM-CSF in vitro in response to heat-killed Kp compared with WT AEC. TLR4lps-d AEC underwent significantly more apoptosis in response to heat-killed Kp in vitro, and treatment with GM-CSF protected these cells from apoptosis in response to Kp. Finally, intratracheal administration of GM-CSF in TLR4lps-d mice significantly decreased albumin leak, lung cell apoptosis, and bacteremia in Kp-infected mice. Based on these observations, we conclude that TLR4 plays a protective role on lung epithelium during Gram-negative bacterial pneumonia, an effect that is partially mediated by GM-CSF.

Bacterial biofilm adherence to middle-ear ventilation tubes: scanning electron micrograph images and literature review

2007 ◽  
Vol 121 (10) ◽  
pp. 993-997 ◽  
Author(s):  
M Barakate ◽  
E Beckenham ◽  
J Curotta ◽  
M da Cruz
Keyword(s):  
Middle Ear ◽  
Bacterial Biofilm ◽  
Electron Micrograph ◽  
Ventilation Tube ◽  
Scanning Electron Micrograph ◽  
Chronic Infections ◽  
Middle Ear Ventilation ◽  
Conventional Antibiotics ◽  
Scanning Electron

Introduction: The organisms that cause many device-related and other chronic infections actually grow in biofilms in or on these devices. We sought to examine the role of biofilm formation in chronic middle-ear ventilation tube infection.Case report: Scanning electron micrograph images are presented which demonstrate biofilm on a middle-ear ventilation tube removed from a five-year-old child's chronically discharging ear. A review of the relevant international literature explores the role of biofilms in chronic infection and discusses potential intervention strategies.Conclusion: Biofilms may be responsible for chronic middle-ear ventilation tube infection that resists treatment with conventional antibiotics.

scholarly journals C/EBPα directs monocytic commitment of primary myeloid progenitors

Blood ◽  
2006 ◽  
Vol 108 (4) ◽  
pp. 1223-1229 ◽  
Author(s):  
Dehua Wang ◽  
Jenice D'Costa ◽  
Curt I. Civin ◽  
Alan D. Friedman
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Fold Increase ◽  
Pcr Assay ◽  
Gm Csf ◽  
Specific Effects ◽  
Proliferation And Apoptosis ◽  
Polymerase Chain ◽  
Lineage Markers ◽  
Transcriptional Induction

Abstract C/EBPα is required for generation of granulocyte-monocyte progenitors, but the subsequent role of C/EBPα in myeloid lineage commitment remains uncertain. We transduced murine marrow cells with C/EBPα-estradiol receptor (ER) or empty vector and subjected these to lineage depletion just prior to culture in estradiol with myeloid cytokines. This protocol limits biases due to lineage-specific effects on developmental kinetics, proliferation, and apoptosis. Also, lowering the dose of estradiol reduced activated C/EBPα-ER to near the physiologic range. C/EBPα-ER increased Mac1+/Gr1–/MPO–/low monocytes 1.9-fold while reducing Mac1+/Gr1+/MPOhi granulocytes 2.5-fold at 48 hours, even in 0.01 μM estradiol. This pattern was confirmed morphologically and by quantitative polymerase chain reaction (PCR) assay of lineage markers. To directly assess effects on immature progenitors, transduced cells were cultured for 1 day with and then in methylcellulose without estradiol. A 2-fold increase in monocytic compared with granulocytic colonies was observed in IL-3/IL-6/SCF or GM-CSF, but not G-CSF, even in 0.01 μM estradiol. C/EBPα-ER induced PU.1 mRNA, and PU.1-ER stimulated monocytic development, suggesting that transcriptional induction of PU.1 by C/EBPα contributes to monopoiesis. A C/EBPα variant incapable of zippering with c-Jun did not induce monopoiesis, and a variant unable to bind NF-κB p50 stimulated granulopoiesis, suggesting their cooperation with C/EBPα during monocytic commitment.

scholarly journals Eosinophil-specific deletion of IκBα in mice reveals a critical role of NF-κB–induced Bcl-xL for inhibition of apoptosis

Blood ◽  
2015 ◽  
Vol 125 (25) ◽  
pp. 3896-3904 ◽  
Author(s):  
Christian Schwartz ◽  
Ralf Willebrand ◽  
Silke Huber ◽  
Rudolf A. Rupec ◽  
Davina Wu ◽  
...  
Keyword(s):  
Helminth Infection ◽  
Critical Role ◽  
Gm Csf ◽  
Eosinophil Survival ◽  
Key Points ◽  
Specific Deletion ◽  
Specific Inhibitors

Key Points IL-3, IL-5, and GM-CSF promote eosinophil survival by NF-κB–induced upregulation of Bcl-xL, which can be blocked by specific inhibitors. Specific and constitutive deletion of the inhibitor of NF-κB (IκBα) in eosinophils in vivo reduced apoptosis during helminth infection.

scholarly journals Generation of Novel Human Red Blood Cell-Bearing Humanized Mouse Models Based on C3-Deficient NOG Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Takuya Yamaguchi ◽  
Ikumi Katano ◽  
Iyo Otsuka ◽  
Ryoji Ito ◽  
Misa Mochizuki ◽  
...  
Keyword(s):  
Mouse Models ◽  
Complement C3 ◽  
Humanized Mouse ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Human Red Blood Cells ◽  
Mouse Macrophages ◽  
C3 Gene ◽  
Humanized Mouse Models

Despite recent advances in immunodeficient mouse models bearing human red blood cells (hRBCs), the elimination of circulating hRBCs by residual innate immune systems remains a significant challenge. In this study, we evaluated the role of mouse complement C3 in the elimination of circulating hRBCs by developing a novel NOG substrain harboring a truncated version of the murine C3 gene (NOG-C3ΔMG2-3). Genetic C3 deletion prolonged the survival of transfused hRBCs in the circulation. Chemical depletion and functional impairment of mouse macrophages, using clodronate liposomes (Clo-lip) or gadolinium chloride (GdCl3), respectively, further extended the survival of hRBCs in NOG-C3ΔMG2-3 mice. Low GdCl3 toxicity allowed the establishment of hRBC-bearing mice, in which hRBCs survived for more than 4 weeks with transfusion once a week. In addition, erythropoiesis of human hematopoietic stem cells (hHSCs) was possible in NOG-C3ΔMG2-3/human GM-CSF-IL-3 transgenic mice with Clo-lip treatment. These findings indicate that mouse models harboring hRBCs can be achieved using NOG-C3ΔMG2-3 mice, which could facilitate studies of human diseases associated with RBCs.

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