scholarly journals Krueppel-Like Factor 4 Expression in Phagocytes Regulates Early Inflammatory Response and Disease Severity in Pneumococcal Pneumonia

2021 ◽  
Vol 12 ◽  
Author(s):  
Toni Herta ◽  
Aritra Bhattacharyya ◽  
Maciej Rosolowski ◽  
Claudia Conrad ◽  
Corinne Gurtner ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Disease Severity ◽  
Pneumococcal Pneumonia ◽  
Myeloid Cells ◽  
Polymorphonuclear Neutrophils ◽  
Therapeutic Interventions ◽  
Intensive Care Unit Treatment ◽  
Inflammatory Immune Response ◽  
The Impact

The transcription factor Krueppel-like factor (KLF) 4 fosters the pro-inflammatory immune response in macrophages and polymorphonuclear neutrophils (PMNs) when stimulated with Streptococcus pneumoniae, the main causative pathogen of community-acquired pneumonia (CAP). Here, we investigated the impact of KLF4 expression in myeloid cells such as macrophages and PMNs on inflammatory response and disease severity in a pneumococcal pneumonia mouse model and in patients admitted to hospital with CAP. We found that mice with a myeloid-specific knockout of KLF4 mount an insufficient early immune response with reduced levels of pro-inflammatory cytokines and increased levels of the anti-inflammatory cytokine interleukin (IL) 10 in bronchoalveolar lavage fluid and plasma and an impaired bacterial clearance from the lungs 24 hours after infection with S. pneumoniae. This results in higher rates of bacteremia, increased lung tissue damage, more severe symptoms of infection and reduced survival. Higher KLF4 gene expression levels in the peripheral blood of patients with CAP at hospital admission correlate with a favourable clinical presentation (lower sequential organ failure assessment (SOFA) score), lower serum levels of IL-10 at admission, shorter hospital stay and lower mortality or requirement of intensive care unit treatment within 28 days after admission. Thus, KLF4 in myeloid cells such as macrophages and PMNs is an important regulator of the early pro-inflammatory immune response and, therefore, a potentially interesting target for therapeutic interventions in pneumococcal pneumonia.

scholarly journals Cannabis and Inflammatory Mediators

2020 ◽  
Vol 27 (1) ◽  
pp. 16-24
Author(s):  
Marcelo G. Lima ◽  
Vitor S. Tardelli ◽  
Elisa Brietzke ◽  
Thiago M. Fidalgo
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
Inflammatory Response ◽  
Healthy Volunteers ◽  
Inflammatory Mediators ◽  
Inflammatory Markers ◽  
Cannabis Use ◽  
Pubmed Database ◽  
Inflammatory Activation ◽  
The Impact

<b><i>Introduction:</i></b> Although the recreational cannabis use is expressive worldwide, the literature about medical potential of cannabis extracts, including its anti-inflammatory properties, remains inconclusive. <b><i>Methods:</i></b> We screened all articles, published on the PubMed database, on inflammatory mediators and any information about cannabis use from 1980 to March 2019. <b><i>Results:</i></b> Six studies were included, and the main findings were as follows: (i) among healthy volunteers and cannabis users, cannabinoids seemed to decrease the inflammatory response, thus decreasing the immune response, which led to a higher risk of infections; (ii) among patients with multiple sclerosis, cannabinoids seemed to have little impact on the inflammatory markers’ levels. <b><i>Discussion:</i></b> Although cannabis use can produce immune inflammatory suppression in healthy people, this effect is not robust enough to change inflammatory mediators’ levels in situations of highly dysfunctional inflammatory activation. Nevertheless, the impact of cannabinoids in clinical outcomes of these conditions remains to be determined.

scholarly journals Microglia: Agents of the CNS Pro-Inflammatory Response

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1717 ◽  
Author(s):  
José A. Rodríguez-Gómez ◽  
Edel Kavanagh ◽  
Pinelopi Engskog-Vlachos ◽  
Mikael K.R. Engskog ◽  
Antonio J. Herrera ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Reactive Microglia ◽  
Holistic View ◽  
Human Microglia ◽  
Positron Emission ◽  
New Research ◽  
The Impact

The pro-inflammatory immune response driven by microglia is a key contributor to the pathogenesis of several neurodegenerative diseases. Though the research of microglia spans over a century, the last two decades have increased our understanding exponentially. Here, we discuss the phenotypic transformation from homeostatic microglia towards reactive microglia, initiated by specific ligand binding to pattern recognition receptors including toll-like receptor-4 (TLR4) or triggering receptors expressed on myeloid cells-2 (TREM2), as well as pro-inflammatory signaling pathways triggered such as the caspase-mediated immune response. Additionally, new research disciplines such as epigenetics and immunometabolism have provided us with a more holistic view of how changes in DNA methylation, microRNAs, and the metabolome may influence the pro-inflammatory response. This review aimed to discuss our current knowledge of pro-inflammatory microglia from different angles, including recent research highlights such as the role of exosomes in spreading neuroinflammation and emerging techniques in microglia research including positron emission tomography (PET) scanning and the use of human microglia generated from induced pluripotent stem cells (iPSCs). Finally, we also discuss current thoughts on the impact of pro-inflammatory microglia in neurodegenerative diseases.

scholarly journals The impact of time on the systemic inflammatory response in pneumococcal pneumonia

2009 ◽  
Vol 35 (3) ◽  
pp. 614-618 ◽  
Author(s):  
E. Calbo ◽  
M. Alsina ◽  
M. Rodriguez-Carballeira ◽  
J. Lite ◽  
J. Garau
Keyword(s):  
Inflammatory Response ◽  
Pneumococcal Pneumonia ◽  
Systemic Inflammatory Response ◽  
The Impact

scholarly journals Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected withParacoccidioides brasiliensis

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Paula Andrea Pino-Tamayo ◽  
Juan David Puerta-Arias ◽  
Damaris Lopera ◽  
Martha Eugenia Urán-Jiménez ◽  
Ángel González
Keyword(s):  
Monoclonal Antibody ◽  
Immune Response ◽  
Inflammatory Response ◽  
Paracoccidioides Brasiliensis ◽  
Yeast Cells ◽  
Histopathological Analysis ◽  
Acute Inflammatory Response ◽  
Fungal Load ◽  
Inflammatory Immune Response

Neutrophils predominate during the acute phase of theParacoccidioides brasiliensisinfection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with1.5×106or2×106P. brasiliensisyeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis. Neutrophils from mAb-treated mice were efficiently depleted (99.04%). Eighty percent of the mice treated with the mAb and infected with1.5×106yeast cells died during the first two weeks after infection. When mice were treated and infected with2×106yeast cells, 100% of them succumbed by the first week after infection. During the acute inflammatory response significant increases in numbers of eosinophils, fungal load and levels of proinflammatory cytokines/chemokines were observed in the mAb-treated mice. We also confirmed that neutrophils are an important source of IFN-γand IL-17. These results indicate that neutrophils are essential for protection as well as being important for regulating the early inflammatory immune response in experimental pulmonary paracoccidioidomycosis.

scholarly journals Aging dampens the intestinal innate immune response during Clostridioides difficile infection and is associated with altered intestinal eosinophil mobilization

2020 ◽  
Author(s):  
Lisa Abernathy-Close ◽  
Michael G. Dieterle ◽  
Kimberly C. Vendrov ◽  
Ingrid L. Bergin ◽  
Vincent B. Young
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Disease Severity ◽  
Advanced Age ◽  
Simultaneous Increase ◽  
Aged Mice ◽  
Age Related ◽  
Cellular Immune ◽  
The Impact ◽  
Young Mice

ABSTRACTClostridioides (formerly Clostridium) difficile is the most common cause of hospital-acquired infection, and advanced age is a risk factor for C. difficile infection. Disruption of the intestinal microbiota and immune responses contribute to host susceptibility and severity of C. difficile infection. However, the impact of aging on the cellular immune response associated with C. difficile infection in the setting of advanced age remains to be well described. This study explores the effect of age on cellular immune responses in C. difficile infection as well as disease severity. Young adult mice (2-3 months old) and aged mice (22-28 months old) were rendered susceptible to C. difficile infection with cefoperazone and then infected with C. difficile strains of varying disease-causing potential. Aged mice infected with C. difficile develop more severe clinical disease, compared to young mice. Tissue-specific CD45+ immune cell responses occurred at the time of peak disease severity in the cecum and colon of all mice infected with a high-virulence strain of C. difficile; however, significant deficits in intestinal neutrophils and eosinophils were detected in aged mice. Interestingly, while C. difficile infection in young mice was associated with a robust increase in cecal and colonic eosinophils, there was a complete lack of an intestinal eosinophil response in aged counterparts accompanied by a simultaneous increase in blood eosinophils with severe disease. These findings demonstrate that age-related alterations in immune responses are associated with significantly worse C. difficile infection and support a key role for intestinal eosinophils in mitigating C. difficile-mediated disease severity.

scholarly journals The impact of the pro- and anti-inflammatory immune response on ventilation time after cardiac surgery

2003 ◽  
Vol 53B (1) ◽  
pp. 70-74 ◽  
Author(s):  
Markus Rothenburger ◽  
Tonny D.T. Tjan ◽  
Michael Schneider ◽  
Elmar Berendes ◽  
Christof Schmid ◽  
...  
Keyword(s):  
Immune Response ◽  
Cardiac Surgery ◽  
Ventilation Time ◽  
Inflammatory Immune Response ◽  
Anti Inflammatory ◽  
The Impact

scholarly journals Hyperinflammation and Immune Response Generation in COVID-19

2020 ◽  
pp. 1-7
Author(s):  
Kamla Prasad Mishra ◽  
Ajay Kumar Singh ◽  
Shashi Bala Singh
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Inflammatory Response ◽  
Disease Severity ◽  
Human Body ◽  
Scientific Community ◽  
The Other ◽  
Complement Proteins ◽  
Cytokines And Chemokines ◽  
Cell Mediated Immune Response

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide. The pathophysiology of this virus is not very clearly known, thus, enormous efforts are being made by the scientific community to delineate its evading mechanism. In this review, we have summarized the hyperinflammation and humoral and cell-mediated immune response generated in human body after infection with the SARS-CoV-2 virus. The inflammatory response generated after infection by increased proinflammatory cytokines and chemokines, and complement proteins activation may likely contribute to disease severity. We also discussed the other factors that may affect immunity and could be important comorbidities in the disease severity and outcome.

scholarly journals Immune Response in Pneumocystis Infections According to the Host Immune System Status

2021 ◽  
Vol 7 (8) ◽  
pp. 625
Author(s):  
Eléna Charpentier ◽  
Sandie Ménard ◽  
Catherine Marques ◽  
Antoine Berry ◽  
Xavier Iriart
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Immune Status ◽  
Pneumocystis Pneumonia ◽  
Favourable Outcome ◽  
Lung Damage ◽  
Host Immune System ◽  
M1 Macrophage ◽  
Immune Deficiencies ◽  
The Impact

The host immune response is critical in Pneumocystis pneumonia (PCP). Immunocompetent hosts can eliminate the fungus without symptoms, while immunodeficient hosts develop PCP with an unsuitable excessive inflammatory response leading to lung damage. From studies based on rodent models or clinical studies, this review aimed to better understand the pathophysiology of Pneumocystis infection by analysing the role of immune cells, mostly lymphocytes, according to the immune status of the infected host. Hence, this review first describes the immune physiological response in infected immunocompetent hosts that are able to eliminate the fungus. The objective of the second part is to identify the immune elements required for the control of the fungus, focusing on specific immune deficiencies. Finally, the third part concentrates on the effect of the different immune elements in immunocompromised subjects during PCP, to better understand which cells are detrimental, and which, on the contrary, are beneficial once the disease has started. This work highlights that the immune response associated with a favourable outcome of the infection may differ according to the immune status of the host. In the case of immunocompetency, a close communication between B cells and TCD4 within tertiary lymphocyte structures appears critical to activate M2 macrophages without much inflammation. Conversely, in the case of immunodeficiency, a pro-inflammatory response including Th1 CD4, cytotoxic CD8, NK cells, and IFNγ release seems beneficial for M1 macrophage activation, despite the impact of inflammation on lung tissue.

scholarly journals RBM15-mediated N6-methyladenosine modification affects COVID-19 severity by regulating the expression of multitarget genes

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Yuting Meng ◽  
Qiong Zhang ◽  
Kaihang Wang ◽  
Xujun Zhang ◽  
Rongwei Yang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Severe Acute Respiratory Syndrome ◽  
Programmed Cell Death ◽  
Inflammatory Response ◽  
Disease Severity ◽  
Biological Processes ◽  
Underlying Mechanisms ◽  
Microarray Analyses

AbstractSevere coronavirus disease 2019 (COVID-19) is characterized by symptoms of lymphopenia and multiorgan damage, but the underlying mechanisms remain unclear. To explore the function of N6-methyladenosine (m6A) modifications in COVID-19, we performed microarray analyses to comprehensively characterize the m6A epitranscriptome. The results revealed distinct global m6A profiles in severe and mild COVID-19 patients. Programmed cell death and inflammatory response were the major biological processes modulated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further, RBM15, a major m6A methyltransferase, was significantly elevated and positively correlated with disease severity. Silencing RBM15 drastically reduced lymphocyte death in vitro. Knockdown of RBM15 remarkably suppressed the expression levels of multitarget genes related to programmed cell death and inflammatory response. This study shows that SARS-CoV-2 infection alters the m6A epitranscriptome of lymphocytes, particularly in the case of severe patients. RBM15 regulated host immune response to SARS-CoV-2 by elevating m6A modifications of multitarget genes. These findings indicate that RBM15 can serve as a target for the treatment of COVID-19.

Sign in / Sign up

Export Citation Format

Share Document