scholarly journals The Role and Mechanism of Pyroptosis and Potential Therapeutic Targets in Sepsis: A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangtao Zheng ◽  
Weiwei Chen ◽  
Fangchen Gong ◽  
Ying Chen ◽  
Erzhen Chen
Keyword(s):  
Immune Response ◽  
Organ Dysfunction ◽  
Host Response ◽  
Therapeutic Targets ◽  
Host Immune Response ◽  
Unique Form ◽  
Pathogen Infection ◽  
Programmed Death ◽  
Life Threatening ◽  
Future Direction

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Recently was been found that pyroptosis is a unique form of proinflammatory programmed death, that is different from apoptosis. A growing number of studies have investigated pyroptosis and its relationship with sepsis, including the mechanisms, role, and relevant targets of pyroptosis in sepsis. While moderate pyroptosis in sepsis can control pathogen infection, excessive pyroptosis can lead to a dysregulated host immune response and even organ dysfunction. This review provides an overview of the mechanisms and potential therapeutic targets underlying pyroptosis in sepsis identified in recent decades, looking forward to the future direction of treatment for sepsis.

Recent advancements of nanomaterial-based therapeutic strategies toward sepsis: bacterial eradication, anti-inflammation, and immunomodulation

Nanoscale ◽  
2021 ◽  
Author(s):  
Yi Zhao ◽  
Minju Pu ◽  
Jingwen Zhang ◽  
Yanan Wang ◽  
Xuefeng Yan ◽  
...  
Keyword(s):  
Immune Response ◽  
Organ Dysfunction ◽  
Tissue Damage ◽  
Host Immune Response ◽  
Therapeutic Strategies ◽  
Bacterial Eradication ◽  
Life Threatening ◽  
Anti Inflammation

Sepsis is a life threatening disease that is caused by a dysregulated host immune response to infection, resulting in tissue damage and organ dysfunction, which account for a high in-hospital...

scholarly journals Cell-Mediated Responses to Human Metapneumovirus Infection

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 542
Author(s):  
Marlies Ballegeer ◽  
Xavier Saelens
Keyword(s):  
Immune Response ◽  
Rna Virus ◽  
Cell Types ◽  
Host Immune Response ◽  
Human Metapneumovirus ◽  
Comprehensive Overview ◽  
Hmpv Infection ◽  
Life Threatening ◽  
Tract Infections ◽  
Almost All

Viruses are the most common cause of acute respiratory tract infections (ARTI). Human metapneumovirus (hMPV) frequently causes viral pneumonia which can become life-threatening if the virus spreads to the lungs. Even though hMPV was only isolated in 2001, this negative-stranded RNA virus has probably been circulating in the human population for many decades. Interestingly, almost all adults have serologic evidence of hMPV infection. A well-established host immune response is evoked when hMPV infection occurs. However, the virus has evolved to circumvent and even exploit the host immune response. Further, infection with hMPV induces a weak memory response, and re-infections during life are common. In this review, we provide a comprehensive overview of the different cell types involved in the immune response in order to better understand the immunopathology induced by hMPV. Such knowledge may contribute to the development of vaccines and therapeutics directed against hMPV.

scholarly journals CXCL5-mediated recruitment of neutrophils into the peritoneal cavity ofGdf15-deficient mice protects against abdominal sepsis

2020 ◽  
Vol 117 (22) ◽  
pp. 12281-12287 ◽  
Author(s):  
Isa Santos ◽  
Henrique G. Colaço ◽  
Ana Neves-Costa ◽  
Elsa Seixas ◽  
Tiago R. Velho ◽  
...  
Keyword(s):  
Septic Shock ◽  
Organ Dysfunction ◽  
Peritoneal Cavity ◽  
Host Response ◽  
Abdominal Sepsis ◽  
Neutrophil Recruitment ◽  
Life Threatening ◽  
Pathogen Control ◽  
Circulating Levels ◽  
Deficient Mice

Sepsis is a life-threatening organ dysfunction condition caused by a dysregulated host response to an infection. Here we report that the circulating levels of growth and differentiation factor-15 (GDF15) are strongly increased in septic shock patients and correlate with mortality. In mice, we find that peptidoglycan is a potent ligand that signals through the TLR2-Myd88 axis for the secretion of GDF15, and thatGdf15-deficient mice are protected against abdominal sepsis due to increased chemokine CXC ligand 5 (CXCL5)-mediated recruitment of neutrophils into the peritoneum, leading to better local bacterial control. Our results identify GDF15 as a potential target to improve sepsis treatment. Its inhibition should increase neutrophil recruitment to the site of infection and consequently lead to better pathogen control and clearance.

Microphallids in Gammarus insensibilis Stock, 1966 from a Black Sea lagoon: host response to infection

Parasitology ◽  
2005 ◽  
Vol 131 (3) ◽  
pp. 347-354 ◽  
Author(s):  
A. KOSTADINOVA ◽  
R. S. MAVRODIEVA
Keyword(s):  
Immune Response ◽  
Wound Healing ◽  
Black Sea ◽  
Host Response ◽  
Host Immune Response ◽  
Abundant Species ◽  
Mediterranean Coast ◽  
Immune Challenges ◽  
Using Data

We examined the patterns of parasite melanization in Gammarus insensibilis using data on microphallids from Pomorie Lagoon (Black Sea) in the light of 3 predictions associated with host survival: (i) hosts invest more in defence in an environment where the likelihood for infection is higher; (ii) multiple immune challenges exhaust host reserves and result in decreased melanization rates in older hosts; (iii) host immune response is directed against the cerebral metacercariae of Microphallus papillorobustus that alter amphipod behaviour and are most detrimental to the host. G. insensibilis was capable of melanizing the metacercariae of all four species of trematodes found to be hosted by the amphipods. The frequency of melanization and mean abundance of melanized metacercariae were substantially higher than those observed in the same amphipod-gammarid system on the French Mediterranean coast. However, the rate of melanization was low and showed a significant decrease with amphipod size. Although the 4 species were differentially melanized, the host response was largely directed against Microphallus hoffmanni and M. subdolum. We suggest that (i) the lower melanization efficiency with age is due to the mode of infection, probably leading to loss of haemolymph and monopolization of the defence resources for wound healing and (ii) in the French system, host response focuses on the most prevalent and abundant species.

scholarly journals An assessment of knowledge and education about sepsis among medical students: a multi-university survey

2021 ◽  
Vol 23 (1) ◽  
pp. 117-118
Author(s):  
Rachit Datta ◽  
◽  
Gian Luca Di Tanna ◽  
Amanda Harley ◽  
Luregn J Schlapbach ◽  
...  
Keyword(s):  
Critical Illness ◽  
Medical Students ◽  
Organ Dysfunction ◽  
Host Response ◽  
Medical Schools ◽  
Junior Doctors ◽  
Life Threatening ◽  
Time Critical ◽  
Australian Universities

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection; it affects 55 000 Australians and results in around 8700 deaths annually.1 Studies have shown that junior doctors have reduced awareness of the importance of sepsis as a time-critical illness.2 Whether this deficiency is a consequence of insufficient training on sepsis in medical schools is unknown. This study evaluated the knowledge of sepsis among medical students in two Australian universities

scholarly journals diagnosis and trEatmEnt of patiEnts in sEptiC shoCK

New Medicine ◽  
2017 ◽  
Vol 21 (1) ◽  
pp. 31-36
Author(s):  
Jacek wadełek
Keyword(s):  
Septic Shock ◽  
Organ Dysfunction ◽  
Host Response ◽  
Signs And Symptoms ◽  
Intravenous Fluids ◽  
Failure Assessment ◽  
Acute Change ◽  
Life Threatening ◽  
Sepsis And Septic Shock ◽  
Clinical Emergency

sepsis and septic shock are a clinical emergency. sepsis is defined as a life-threatening organ dysfunction due to a dysregulated host response to infection, and organ dysfunction is defined as an acute change in sequential organ failure assessment (sofa) score greater than 2 points secondary to an infectious cause. septic shock is defined as sepsis with persisting hypotension requiring vasopressors to maintain a mean arterial pressure of 65 mm hg or higher, and blood lactate level greater than 2 mmol/l (18 mg/dl) despite adequate volume resuscitation. the diagnosis of septic shock begins with medical history and physical examination focused on the signs and symptoms of infection, with the aim of recognizing complex physiologic manifestations of shock. Clinicians should understand the importance of prompt administration of antibiotics, vasopressors and intravenous fluids aimed at restoring adequate circulation. they should also be aware of the limitations of the protocol-based therapy.

scholarly journals Recent application of metabolomics in the diagnosis, pathogenesis, treatment, and prognosis of sepsis

2021 ◽  
Keyword(s):  
Early Diagnosis ◽  
Organ Dysfunction ◽  
Host Response ◽  
Clinical Manifestations ◽  
Rapid Diagnosis ◽  
Pathophysiological Mechanism ◽  
Recent Application ◽  
Biochemical Pathways ◽  
Diagnosis And Prognosis ◽  
Life Threatening

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infections. It is a leading cause of morbidity and mortality in hospitalized patients. Patients with sepsis often require care in the intensive care unit (ICU) which is costly to the patients and their families. Sepsis has no specific clinical manifestations, and its pathophysiological mechanism is complex. The disease progresses rapidly which makes early diagnosis difficult. Severe forms of the disease, such as septic shock, may lead to organ dysfunction, organ failure, and death. As an emerging “-omics” technology, metabolomics has revolutionized the clinical and research landscape of sepsis. Metabolomics has been applied in the prognosis, diagnosis, and risk stratification in patients with sepsis. This technology provides details on the metabolites and biochemical pathways commonly associated with the pathophysiology of sepsis. At present, it is mostly used to identify metabolites in various diseases. Using this technology, metabolites in body fluids such as blood and urine are detected and analyzed in relation to disease progresssion. The technology therefore helps to understand the pathogenesis of diseases and promote early diagnosis and treatment of the disease. So far, the applicaition of metabolomics in patients with sepsis has not been well defined. This article briefly reviews the application of metabolomics technology in patients with sepsis in recent years, to generate ideas for improving rapid diagnosis and prognosis evaluation of patients with sepsis.

Blood leukocyte transcriptomes in gram-positive and gram-negative community-acquired pneumonia

2021 ◽  
pp. 2101856
Author(s):  
Liza Pereverzeva ◽  
Fabrice Uhel ◽  
Hessel Peters Sengers ◽  
Joe Butler ◽  
Lonneke A. van Vught ◽  
...  
Keyword(s):  
Immune Response ◽  
Host Response ◽  
Host Immune Response ◽  
Community Acquired Pneumonia ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Icu Admission ◽  
Blood Leukocyte ◽  
Response Biomarkers

BackgroundGram-positive and Gram-negative bacteria are the most common causative pathogens in community-acquired pneumonia (CAP) on the intensive care unit (ICU). The aim of this study was to determine whether the host immune response differs between Gram-positive and Gram-negative CAP upon ICU admission.MethodsSixteen host response biomarkers providing insight in pathophysiological mechanisms implicated in sepsis and blood leukocyte transcriptomes were analysed in patients with CAP upon ICU admission in two tertiary hospitals in the Netherlands.Results309 patients with CAP with a definite or probable likelihood (determined by predefined criteria) were included. A causative pathogen was determined in 74.4% of admissions. Patients admitted with Gram-positive CAP (n=90) were not different from those admitted with Gram-negative CAP (n=75) regarding demographics, chronic comorbidities, severity of disease and mortality. Host response biomarkers reflective of systemic inflammation, coagulation activation and endothelial cell function, as well as blood leukocytes transcriptomes, were largely similar between Gram-positive and Gram-negative CAP. Blood leukocyte transcriptomes were also similar in Gram-positive and Gram-negative CAP in two independent validation cohorts. On a pathogen-specific level, Streptococcus pneumoniae and Escherichia coli induced the most distinct host immune response.ConclusionOutcome and host response are similar in critically ill patients with CAP due to Gram-positive bacteria compared to Gram-negative bacteria.

scholarly journals Pathologic Difference between Sepsis and Bloodstream Infections

2019 ◽  
Vol 3 (4) ◽  
pp. 654-663 ◽  
Author(s):  
Luis E Huerta ◽  
Todd W Rice
Keyword(s):  
Mitochondrial Dysfunction ◽  
Organ Dysfunction ◽  
Host Response ◽  
Laboratory Tests ◽  
Bloodstream Infections ◽  
Therapeutic Interventions ◽  
Coagulation Cascade ◽  
Sepsis Diagnosis ◽  
Reactive Protein ◽  
Life Threatening

Abstract Background Sepsis, defined as life-threatening organ failure caused by a dysregulated host response to infection, is a major cause of morbidity and mortality in hospitalized patients. Understanding the features that distinguish sepsis from bloodstream infections (and other types of infection) can help clinicians appropriately and efficiently target their diagnostic workup and therapeutic interventions, especially early in the disease course. Content In this review, sepsis and bloodstream infections are both defined, with a focus on recent changes in the sepsis definition. The molecular and cellular pathways involved in sepsis pathogenesis are described, including cytokines, the coagulation cascade, apoptosis, and mitochondrial dysfunction. Laboratory tests that have been evaluated for their utility in sepsis diagnosis are discussed. Summary Sepsis is defined not only by the presence of an infection, but also by organ dysfunction from a dysregulated host response to that infection. Numerous pathways, including proinflammatory and antiinflammatory cytokines, the coagulation cascade, apoptosis, and mitochondrial dysfunction, help determine if a bloodstream infection (or any other infection) progresses to sepsis. Many biomarkers, including C-reactive protein, procalcitonin, and lactic acid have been evaluated for use in sepsis diagnosis, although none are routinely recommended for that purpose in current clinical practice. While some laboratory tests can help distinguish the 2, the presence of organ dysfunction is what separates sepsis from routine infections.

scholarly journals Extracellular Vesicles: A Double-Edged Sword in Sepsis

2021 ◽  
Vol 14 (8) ◽  
pp. 829
Author(s):  
Marlies Burgelman ◽  
Charysse Vandendriessche ◽  
Roosmarijn E. Vandenbroucke
Keyword(s):  
Clinical Outcome ◽  
Organ Dysfunction ◽  
Extracellular Vesicles ◽  
Host Response ◽  
Current Knowledge ◽  
Healthy Controls ◽  
Lymphocyte Apoptosis ◽  
Cellular Source ◽  
Life Threatening

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Several studies on mouse and patient sepsis samples have revealed that the level of extracellular vesicles (EVs) in the blood is altered compared to healthy controls, but the different functions of EVs during sepsis pathology are not yet completely understood. Sepsis EVs are described as modulators of inflammation, lymphocyte apoptosis, coagulation and organ dysfunction. Furthermore, EVs can influence clinical outcome and it is suggested that EVs can predict survival. Both detrimental and beneficial roles for EVs have been described in sepsis, depending on the EV cellular source and the disease phase during which the EVs are studied. In this review, we summarize the current knowledge of EV sources and functions during sepsis pathology based on in vitro and mouse models, as well as patient samples.

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