scholarly journals The Understanding and Management of Organism Toxicity in Septic Shock

2018 ◽  
Vol 10 (5-6) ◽  
pp. 502-514 ◽  
Author(s):  
Kelly Roveran Genga ◽  
Tadanaga Shimada ◽  
John H. Boyd ◽  
Keith R. Walley ◽  
James A. Russell
Keyword(s):  
Septic Shock ◽  
Immune Responses ◽  
Host Response ◽  
Therapeutic Strategies ◽  
Organ Injury ◽  
Inflammasome Activation ◽  
Current Therapies ◽  
Subsequent Activation ◽  
Molecular Patterns

The toxicity caused by different organisms in septic shock is substantially complex and characterized by an intricate pathogenicity that involves several systems and pathways. Immune cells’ pattern recognition receptors initiate the host response to pathogens after the recognition of pathogen-associated molecular patterns. In essence, the subsequent activation of downstream pathways may progress to infection resolution or to a dysregulated host response that represents the hallmark of organ injury in septic shock. Likewise, the management of organism toxicity in septic shock is complicated and comprises a multiplicity of suitable targets. In this review, the classic immune responses to pathogens are discussed as well as other factors that are relevant in the pathogenicity of septic shock, including sepsis-induced immune suppression, inflammasome activation, intestinal permeability, and the role of lipids and proprotein convertase subtilisin/kexin type 9. Current therapies aiming to eliminate the organisms causing septic shock, recent and ongoing trials in septic shock treatment, and potential new therapeutic strategies are also explored.

scholarly journals The Role of Macrophages in the Host’s Defense against Sporothrix schenckii

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 905
Author(s):  
Estela Ruiz-Baca ◽  
Armando Pérez-Torres ◽  
Yolanda Romo-Lozano ◽  
Daniel Cervantes-García ◽  
Carlos A. Alba-Fierro ◽  
...  
Keyword(s):  
Immune Responses ◽  
Macrophage Polarization ◽  
Sporothrix Schenckii ◽  
Macrophage Cell ◽  
Cell Recruitment ◽  
Host Pathogen Interaction ◽  
Interaction Processes ◽  
Host Pathogen ◽  
Molecular Patterns

The role of immune cells associated with sporotrichosis caused by Sporothrix schenckii is not yet fully clarified. Macrophages through pattern recognition receptors (PRRs) can recognize pathogen-associated molecular patterns (PAMPs) of Sporothrix, engulf it, activate respiratory burst, and secrete pro-inflammatory or anti-inflammatory biological mediators to control infection. It is important to consider that the characteristics associated with S. schenckii and/or the host may influence macrophage polarization (M1/M2), cell recruitment, and the type of immune response (1, 2, and 17). Currently, with the use of new monocyte-macrophage cell lines, it is possible to evaluate different host–pathogen interaction processes, which allows for the proposal of new mechanisms in human sporotrichosis. Therefore, in order to contribute to the understanding of these host–pathogen interactions, the aim of this review is to summarize and discuss the immune responses induced by macrophage-S. schenckii interactions, as well as the PRRs and PAMPs involved during the recognition of S. schenckii that favor the immune evasion by the fungus.

scholarly journals Inflammasomes inMycobacterium tuberculosis-Driven Immunity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Sebastian Wawrocki ◽  
Magdalena Druszczynska
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Response ◽  
Immune Responses ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Protein Complexes ◽  
Inflammasome Activation ◽  
Host Immune Responses ◽  
Multimeric Protein

The development of effective innate and subsequent adaptive host immune responses is highly dependent on the production of proinflammatory cytokines that increase the activity of immune cells. The key role in this process is played by inflammasomes, multimeric protein complexes serving as a platform for caspase-1, an enzyme responsible for proteolytic cleavage of IL-1βand IL-18 precursors. Inflammasome activation, which triggers the multifaceted activity of these two proinflammatory cytokines, is a prerequisite for developing an efficient inflammatory response against pathogenicMycobacterium tuberculosis(M.tb). This review focuses on the role of NLRP3 and AIM2 inflammasomes inM.tb-driven immunity.

Role of pathogen-associated molecular patterns (PAMPS) in immune responses to fungal infections

2017 ◽  
Vol 808 ◽  
pp. 8-13 ◽  
Author(s):  
Mehdi Taghavi ◽  
Alireza Khosravi ◽  
Esmaeil Mortaz ◽  
Donya Nikaein ◽  
Seyyed Shamsadin Athari
Keyword(s):  
Immune Responses ◽  
Fungal Infections ◽  
Molecular Patterns

Heparin-based blood purification attenuates organ injury in baboons with S. pneumoniae pneumonia

2021 ◽  
Author(s):  
Lingye Chen ◽  
Bryan D Kraft ◽  
Victor L Roggli ◽  
Zachary R Healy ◽  
Christopher W Woods ◽  
...  
Keyword(s):  
Septic Shock ◽  
Pneumococcal Pneumonia ◽  
Kidney Injury ◽  
Blood Purification ◽  
Dose Finding ◽  
Organ Injury ◽  
Inflammasome Activation ◽  
Post Inoculation ◽  
Extracorporeal Blood ◽  
Extracorporeal Blood Purification

Background: Bacterial pneumonia is a major cause of morbidity and mortality worldwide despite the use of antibiotics, and novel therapies are urgently needed. Building on previous work, we aimed to 1) develop a baboon model of severe pneumococcal pneumonia and sepsis with organ dysfunction; and 2) test the safety and efficacy of a novel extracorporeal blood filter to remove pro-inflammatory molecules and improve organ function. Methods: After a dose-finding pilot study, twelve animals were inoculated with S. pneumoniae (5x109 CFU), given ceftriaxone at 24 hours post-inoculation, and randomized to extracorporeal blood purification using a filter coated with surface-immobilized heparin sulfate (n=6) or sham treatment (n=6) for 4 hours at 30 hours post-inoculation. For safety analysis, four uninfected animals also underwent purification. At 48 hours, necropsy was performed. Results: Inoculated animals developed severe pneumonia and septic shock. Compared with sham animals, septic animals treated with purification displayed significantly less kidney injury, metabolic acidosis, hypoglycemia, and shock (P<0.05). Purification blocked the rise in peripheral blood S. pneumoniae DNA, attenuated BAL CCL4, CCL2, and IL-18 levels, and reduced renal oxidative injury and classical NLRP3-inflammasome activation. Purification was safe in both uninfected and infected animals and produced no adverse effects. Conclusions: We demonstrate that heparin-based blood purification significantly attenuates levels of circulating S. pneumoniae DNA and BAL cytokines, and is renal-protective in baboons with severe pneumococcal pneumonia and septic shock. Purification was associated with less severe acute kidney injury, metabolic derangements, and shock. These results support future clinical studies in critically ill septic patients.

scholarly journals Caspase-8 mediates inflammation and disease in rodent malaria

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Larissa M. N. Pereira ◽  
Patrícia A. Assis ◽  
Natalia M. de Araújo ◽  
Danielle F. Durso ◽  
Caroline Junqueira ◽  
...  
Keyword(s):  
Septic Shock ◽  
Human Disease ◽  
Caspase 8 ◽  
Inflammasome Activation ◽  
Plasmodium Chabaudi ◽  
Experimental Cerebral Malaria ◽  
Rodent Malaria ◽  
Canonical Pathways ◽  
Inflammatory Caspases

Abstract Earlier studies indicate that either the canonical or non-canonical pathways of inflammasome activation have a limited role on malaria pathogenesis. Here, we report that caspase-8 is a central mediator of systemic inflammation, septic shock in the Plasmodium chabaudi-infected mice and the P. berghei-induced experimental cerebral malaria (ECM). Importantly, our results indicate that the combined deficiencies of caspases-8/1/11 or caspase-8/gasdermin-D (GSDM-D) renders mice impaired to produce both TNFα and IL-1β and highly resistant to lethality in these models, disclosing a complementary, but independent role of caspase-8 and caspases-1/11/GSDM-D in the pathogenesis of malaria. Further, we find that monocytes from malaria patients express active caspases-1, -4 and -8 suggesting that these inflammatory caspases may also play a role in the pathogenesis of human disease.

NF-κB activation as a pathological mechanism of septic shock and inflammation

2006 ◽  
Vol 290 (4) ◽  
pp. L622-L645 ◽  
Author(s):  
Shu Fang Liu ◽  
Asrar B. Malik
Keyword(s):  
Septic Shock ◽  
Human Subjects ◽  
Myocardial Dysfunction ◽  
Multiple Organ ◽  
Organ Injury ◽  
Pathological Mechanism ◽  
Proinflammatory Gene ◽  
Intensive Investigation ◽  
Sepsis And Septic Shock

The pathophysiology of sepsis and septic shock involves complex cytokine and inflammatory mediator networks. NF-κB activation is a central event leading to the activation of these networks. The role of NF-κB in septic pathophysiology and the signal transduction pathways leading to NF-κB activation during sepsis have been an area of intensive investigation. NF-κB is activated by a variety of pathogens known to cause septic shock syndrome. NF-κB activity is markedly increased in every organ studied, both in animal models of septic shock and in human subjects with sepsis. Greater levels of NF-κB activity are associated with a higher rate of mortality and worse clinical outcome. NF-κB mediates the transcription of exceptional large number of genes, the products of which are known to play important roles in septic pathophysiology. Mice deficient in those NF-κB-dependent genes are resistant to the development of septic shock and to septic lethality. More importantly, blockade of NF-κB pathway corrects septic abnormalities. Inhibition of NF-κB activation restores systemic hypotension, ameliorates septic myocardial dysfunction and vascular derangement, inhibits multiple proinflammatory gene expression, diminishes intravascular coagulation, reduces tissue neutrophil influx, and prevents microvascular endothelial leakage. Inhibition of NF-κB activation prevents multiple organ injury and improves survival in rodent models of septic shock. Thus NF-κB activation plays a central role in the pathophysiology of septic shock.

scholarly journals Phagocytosis: A Fundamental Process in Immunity

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Carlos Rosales ◽  
Eileen Uribe-Querol
Keyword(s):  
Immune Responses ◽  
Host Response ◽  
Current Knowledge ◽  
General View ◽  
Cellular Mechanisms ◽  
Complex Process ◽  
Fundamental Process ◽  
Target Particle ◽  
Acquired Immune Responses

One hundred years have passed since the death of Élie Metchnikoff (1845–1916). He was the first to observe the uptake of particles by cells and realized the importance of this process for the host response to injury and infection. He also was a strong advocate of the role of phagocytosis in cellular immunity, and with this he gave us the basis for our modern understanding of inflammation and the innate and acquired immune responses. Phagocytosis is an elegant but complex process for the ingestion and elimination of pathogens, but it is also important for the elimination of apoptotic cells and hence fundamental for tissue homeostasis. Phagocytosis can be divided into four main steps: (i) recognition of the target particle, (ii) signaling to activate the internalization machinery, (iii) phagosome formation, and (iv) phagolysosome maturation. In recent years, the use of new tools of molecular biology and microscopy has provided new insights into the cellular mechanisms of phagocytosis. In this review, we present a general view of our current knowledge on phagocytosis. We emphasize novel molecular findings, particularly on phagosome formation and maturation, and discuss aspects that remain incompletely understood.

The host response to infection in the critically ill

2016 ◽  
Author(s):  
W. Joost Wiersinga ◽  
Tom van der Poll
Keyword(s):  
Critically Ill ◽  
Host Response ◽  
Inflammatory Responses ◽  
Coagulation Cascade ◽  
Microbial Infection ◽  
Pathogen Invasion ◽  
New Therapeutic Approaches ◽  
Microbial Invasion ◽  
Molecular Patterns

Infection continues to be a leading cause of intensive care unit death. The host response to infection can be seen as a pattern recognition receptor (PRR)-mediated dysregulation of the immune system following pathogen invasion in which a careful balance between inflammatory and anti-inflammatory responses is vital. A measured and rapid response to microbial invasion is essential to health. The same immunological and coagulation systems that protect against localized infection can act to our disadvantage when these systems are activated systemically during generalized microbial infection. Toll-like receptors (TLR), the inflammasomes and other PRRs initiate the host response after recognition of pathogen-associated-molecular-patterns (PAMPs) or endogenous danger-associated-molecular-patterns (DAMPs). The systemic host response to infection will result in activation of coagulation, downregulation of physiological anticoagulant mechanisms, and inhibition of fibrinolysis. Further dissection of the role of host–pathogen interactions, the cytokine response, the coagulation cascade and their multidirectional interactions in sepsis should lead towards the development of new therapeutic approaches in the critically ill who are faced with infection.

scholarly journals The Role of Peptide Signals Hidden in the Structure of Functional Proteins in Plant Immune Responses

2019 ◽  
Vol 20 (18) ◽  
pp. 4343 ◽  
Author(s):  
Irina Lyapina ◽  
Anna Filippova ◽  
Igor Fesenko
Keyword(s):  
Immune Responses ◽  
Defense Responses ◽  
Innate Immune ◽  
Functional Protein ◽  
Diverse Range ◽  
Peptide Signals ◽  
Plant Pathogen Interactions ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Plants have evolved a sophisticated innate immune system to cope with a diverse range of phytopathogens and insect herbivores. Plasma-membrane-localized pattern recognition receptors (PRRs), such as receptor-like kinases (RLK), recognize special signals, pathogen- or damage-associated molecular patterns (PAMPs or DAMPs), and trigger immune responses. A growing body of evidence shows that many peptides hidden in both plant and pathogen functional protein sequences belong to the group of such immune signals. However, the origin, evolution, and release mechanisms of peptide sequences from functional and nonfunctional protein precursors, known as cryptic peptides, are largely unknown. Various special proteases, such as metacaspase or subtilisin-like proteases, are involved in the release of such peptides upon activation during defense responses. In this review, we discuss the roles of cryptic peptide sequences hidden in the structure of functional proteins in plant defense and plant-pathogen interactions.

scholarly journals A20 Promotes Ripoptosome Formation and TNF-Induced Apoptosis via cIAPs Regulation and NIK Stabilization in Keratinocytes

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 351 ◽  
Author(s):  
Maria Feoktistova ◽  
Roman Makarov ◽  
Sihem Brenji ◽  
Anne T. Schneider ◽  
Guido J. Hooiveld ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Skin Diseases ◽  
Signaling Mechanism ◽  
Protein Levels ◽  
Genome Wide ◽  
Multiple Levels ◽  
Subsequent Activation ◽  
Induced Apoptosis

The ubiquitin-editing protein A20 (TNFAIP3) is a known key player in the regulation of immune responses in many organs. Genome-wide associated studies (GWASs) have linked A20 with a number of inflammatory and autoimmune disorders, including psoriasis. Here, we identified a previously unrecognized role of A20 as a pro-apoptotic factor in TNF-induced cell death in keratinocytes. This function of A20 is mediated via the NF-κB-dependent alteration of cIAP1/2 expression. The changes in cIAP1/2 protein levels promote NIK stabilization and subsequent activation of noncanonical NF-κB signaling. Upregulation of TRAF1 expression triggered by the noncanonical NF-κB signaling further enhances the NIK stabilization in an autocrine manner. Finally, stabilized NIK promotes the formation of the ripoptosome and the execution of cell death. Thus, our data demonstrate that A20 controls the execution of TNF-induced cell death on multiple levels in keratinocytes. This signaling mechanism might have important implications for the development of new therapeutic strategies for the treatment of A20-associated skin diseases.

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