scholarly journals Toll-like receptor 9 inhibition reduces mortality in polymicrobial sepsis

2008 ◽  
Vol 205 (6) ◽  
pp. 1277-1283 ◽  
Author(s):  
George Plitas ◽  
Bryan M. Burt ◽  
Hoang M. Nguyen ◽  
Zubin M. Bamboat ◽  
Ronald P. DeMatteo
Keyword(s):  
Immune Response ◽  
Critical Role ◽  
Cecal Ligation ◽  
High Rate ◽  
Microbial Pathogens ◽  
Lower Serum ◽  
Human Sepsis ◽  
Cytokine Levels ◽  
Potential Strategy

The high rate of mortality in patients with sepsis results from an inappropriately amplified systemic inflammatory response to infection. Toll-like receptors (TLRs) are important for the activation of innate immunity against microbial pathogens. We demonstrate a critical role of TLR9 in the dysregulated immune response and death associated with sepsis. Compared with wild-type (WT) mice, TLR9−/− mice exhibited lower serum inflammatory cytokine levels, higher bacterial clearance, and greater survival after experimental peritonitis induced by cecal ligation and puncture (CLP). Protection of TLR9−/− mice after CLP was associated with a greater number of peritoneal dendritic cells (DCs) and granulocytes than in WT controls. Adoptive transfer of TLR9−/− DCs was sufficient to protect WT mice from CLP and increased the influx of peritoneal granulocytes. Subsequent experiments with a depleting antibody revealed that granulocytes were required for survival in TLR9−/− mice. Remarkably, a single injection of an inhibitory CpG sequence that blocks TLR9 protected WT mice, even when administered as late as 12 h after CLP. Our findings demonstrate that the detrimental immune response to bacterial sepsis occurs via TLR9 stimulation. TLR9 blockade is a potential strategy for the treatment of human sepsis.

scholarly journals NLRP7 Promotes Choriocarcinoma Growth and Progression through the Establishment of an Immunosuppressive Microenvironment

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  
Keyword(s):  
Immune Response ◽  
Tumor Cells ◽  
Major Gene ◽  
Critical Role ◽  
Orthotopic Model ◽  
Independent Manner ◽  
Maternal Immune Response ◽  
The Impact

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.

scholarly journals Crosstalk between Dendritic Cells and Immune Modulatory Agents against Sepsis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 323 ◽  
Author(s):  
Guoying Wang ◽  
Xianghui Li ◽  
Lei Zhang ◽  
Abualgasim Elgaili Abdalla ◽  
Tieshan Teng ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Th2 Responses ◽  
Novel Strategy

Dendritic cells (DCs) play a critical role in the immune system which sense pathogens and present their antigens to prime the adaptive immune responses. As the progression of sepsis occurs, DCs are capable of orchestrating the aberrant innate immune response by sustaining the Th1/Th2 responses that are essential for host survival. Hence, an in-depth understanding of the characteristics of DCs would have a beneficial effect in overcoming the obstacle occurring in sepsis. This paper focuses on the role of DCs in the progression of sepsis and we also discuss the reverse sepsis-induced immunosuppression through manipulating the DC function. In addition, we highlight some potent immunotherapies that could be used as a novel strategy in the early treatment of sepsis.

scholarly journals Intermittent fasting, a possible priming tool for host defense against SARS-CoV-2 infection: crosstalk among calorie restriction, autophagy and immune response

2020 ◽  
Author(s):  
Md. Abdul Hannan ◽  
Rahaman ◽  
Saidur Rahman ◽  
Abdullah Al Mamun Sohag ◽  
Raju Dash ◽  
...  
Keyword(s):  
Immune Response ◽  
Host Defense ◽  
Calorie Restriction ◽  
Intermittent Fasting ◽  
Preventive Strategy ◽  
Clinical Settings ◽  
A Cell ◽  
Potential Strategy ◽  
Immunomodulatory Potential

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of deadly Coronavirus disease-19 (COVID-19) pandemic, which emerged as a major threat to public health across the world. Although there is no clear gender or socioeconomic discrimination in the incidence of COVID-19, individuals who are older adults and/or with comorbidities and compromised immunity have a relatively higher risk of contracting this disease. Since no specific drug has yet been discovered, strengthening immunity along with maintaining a healthy living is the best way to survive this disease. As a healthy practice, calorie restriction in the form of intermittent fasting in several clinical settings has been reported to promote several health benefits, including priming of the immune response. This dietary practice also activates autophagy, a cell surveillance system that boosts up immunity. With these prevailing significance in priming host defense, intermittent fasting could be a potential strategy amid this outbreak to fighting off SARS-CoV-2 infection. Currently, no review so far available proposing intermittent fasting as an encouraging strategy in the prevention of COVID-19. A comprehensive review has therefore been planned to highlight the beneficial role of fasting in immunity and autophagy, that underlie the possible defense against SARS-CoV-2 infection. The COVID-19 pathogenesis and its impact on host immune response have also been briefly outlined. This review aimed at revisiting the immunomodulatory potential of intermittent fasting that may constitute a promising preventive strategy against COVID-19.

COVID-19: Inflammatory Profile

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Yuhang Wang ◽  
Stanley Perlman
Keyword(s):  
Immune Response ◽  
Distress Syndrome ◽  
Multiorgan Failure ◽  
Critical Role ◽  
Host Immune Response ◽  
Immune Dysregulation ◽  
Annual Review ◽  
Publication Date ◽  
Inflammatory Profile

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has resulted in a pandemic that has had widespread effects on human activities. The clinical presentation of severe COVID-19 includes a broad spectrum of clinical disease, most notably acute respiratory distress syndrome, cytokine release syndrome (CRS), multiorgan failure, and death. Direct viral damage and uncontrolled inflammation have been suggested as contributory factors in COVID-19 disease severity. The COVID-19 pandemic has emphasized the critical role of an effective host immune response in controlling a virus infection and demonstrated the devastating effect of immune dysregulation. Understanding the nature of the immune response to SARS-CoV-2 pathogenesis is key to developing effective treatments for COVID-19. Here, we describe the nature of the dysregulated host immune response in COVID-19, identify potential mechanisms involved in CRS, and discuss potential strategies that can be used to manage immune dysregulation in COVID-19. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Critical Role of cRel Subunit of NF-κB in Sepsis Survival

2011 ◽  
Vol 79 (5) ◽  
pp. 1848-1854 ◽  
Author(s):  
Emilie Courtine ◽  
Frédéric Pène ◽  
Nicolas Cagnard ◽  
Julie Toubiana ◽  
Catherine Fitting ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Critical Role ◽  
Cecal Ligation ◽  
Gene Expression Profiles ◽  
Severe Infection ◽  
A Genome ◽  
Underlying Mechanisms ◽  
Pathogen Clearance

ABSTRACTNF-κB is a critical regulator of gene expression during severe infections. NF-κB comprises homo- and heterodimers of proteins from the Rel family. Among them, p50 and p65 have been clearly implicated in the pathophysiology of sepsis. In contrast, the role of cRel in sepsis is still controversial and has been poorly studied in single-pathogen infections. We aimed to investigate the consequences of cRel deficiency in a cecal ligation and puncture (CLP) model of sepsis. We have approached the underlying mechanisms of host defense by analyzing bacterial clearance, systemic inflammation, and the distribution of spleen dendritic cell subsets. Moreover, by using a genome-wide technology, we have also analyzed the CLP-induced modifications in gene expression profiles both in wild-type (wt) and inrel−/−mice. The absence of cRel enhances mortality due to polymicrobial sepsis. Despite normal pathogen clearance, cRel deficiency leads to an altered systemic inflammatory response associated with a sustained loss of the spleen lymphoid dendritic cells. Furthermore, a whole-blood microarray study reveals that the differential outcome between wt andrel−/−mice during sepsis is preceded by remarkable changes in the expression of hundreds of genes involved in aspects of host-pathogen interaction, such as host survival and lipid metabolism. In conclusion, cRel is a key NF-κB member required for host antimicrobial defenses and a regulatory transcription subunit that controls the inflammatory and immune responses in severe infection.

scholarly journals Platelets Are Critical Key Players in Sepsis

2019 ◽  
Vol 20 (14) ◽  
pp. 3494 ◽  
Author(s):  
Fanny Vardon-Bounes ◽  
Stéphanie Ruiz ◽  
Marie-Pierre Gratacap ◽  
Cédric Garcia ◽  
Bernard Payrastre ◽  
...  
Keyword(s):  
Immune Response ◽  
Endothelial Cells ◽  
Inflammatory Response ◽  
Host Defense ◽  
Critical Role ◽  
Therapeutic Implications ◽  
Key Players

Host defense against infection is based on two crucial mechanisms: the inflammatory response and the activation of coagulation. Platelets are involved in both hemostasis and immune response. These mechanisms work together in a complex and synchronous manner making the contribution of platelets of major importance in sepsis. This is a summary of the pathophysiology of sepsis-induced thrombocytopenia, microvascular consequences, platelet-endothelial cells and platelet–pathogens interactions. The critical role of platelets during sepsis and the therapeutic implications are also reviewed.

scholarly journals Role of TNF-Alpha, IFN-Gamma, and IL-10 in the Development of Pulmonary Tuberculosis

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Yone Vila Nova Cavalcanti ◽  
Maria Carolina Accioly Brelaz ◽  
Juliana Kelle de Andrade Lemoine Neves ◽  
José Candido Ferraz ◽  
Valéria Rêgo Alves Pereira
Keyword(s):  
Immune Response ◽  
Protective Immunity ◽  
Critical Role ◽  
Tnf Alpha ◽  
Infection Site ◽  
Ifn Gamma ◽  
Major Function ◽  
Reactive Nitrogen Intermediates ◽  
Th1 And Th2 Responses

Host immune response againstMycobacterium tuberculosisis mediated by cellular immunity, in which cytokines and Th1 cells play a critical role. In the process of control of the infection by mycobacteria, TNF-alpha seems to have a primordial function. This cytokine acts in synergy with IFN-gamma, stimulating the production of reactive nitrogen intermediates (RNIs), thus mediating the tuberculostatic function of macrophages, and also stimulating the migration of immune cells to the infection site, contributing to granuloma formation, which controls the disease progression. IFN-gamma is the main cytokine involved in the immune response against mycobacteria, and its major function is the activation of macrophages, allowing them to exert its microbicidal role functions. Different from TNF-alpha and IFN-gamma, IL-10 is considered primarily an inhibitory cytokine, important to an adequate balance between inflammatory and immunopathologic responses. The increase in IL-10 levels seems to support the survival of mycobacteria in the host. Although there is not yet conclusive studies concerning a clear dichotomy between Th1 and Th2 responses, involving protective immunity and susceptibility to the disease, respectively, we can suggest that the knowledge about this responses based on the prevailing cytokine profile can help to elucidate the immune response related to the protection againstM. tuberculosis.

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