Facing stress and inflammation: From the cell to the planet.

As identified in 1936 by Hans Selye, stress is shaping diseases through the induction of inflammation. But inflammation display some yin yang properties. On one hand inflammation is merging with the innate immune response aimed to fight infectious or sterile insults, on the other hand inflammation favors chronic physical or psychological disorders.

Divergent effects of tumor necrosis factor (TNF) in sepsis: a meta-analysis of experimental studies.

Introduction: Experimental studies in animals have yielded conflicting results on the role of Tumor Necrosis Factor (TNF) in sepsis and endotoxemia, with some reporting adaptive and others inappropriate effects. A meta-analysis of the available literature was performed to determine the factors explaining this discrepancy.

Methods: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Compartmentalization of the inflammatory response during bacterial sepsis and severe COVID-19.

Acute infections cause local and systemic disorders which can lead in the most severe forms to multi-organ failure and eventually to death. The host response to infection encompasses a large spectrum of reactions with a concomitant activation of the so-called inflammatory response aimed at fighting the infectious agent and removing damaged tissues or cells, and the anti-inflammatory response aimed at controlling inflammation and initiating the healing process. Fine-tuning at the local and systemic levels is key to preventing local and remote injury due to immune system activation.

Profiling the dysregulated immune response in sepsis: overcoming challenges to achieve the goal of precision medicine.

Sepsis is characterised by a dysregulated host immune response to infection. Despite recognition of its significance, immune status monitoring is not implemented in clinical practice due in part to the current absence of direct therapeutic implications. Technological advances in immunological profiling could enhance our understanding of immune dysregulation and facilitate integration into clinical practice.

The dangerous liaisons in innate immunity involving recombinant proteins and endotoxins: Examples from the literature and the Leptospira field.

Endotoxins, also known as lipopolysaccharides (LPS), are essential components of cell walls of diderm bacteria such as Escherichia coli. LPS are microbe-associated molecular patterns that can activate pattern recognition receptors. While trying to investigate the interactions between proteins and host innate immunity, some studies using recombinant proteins expressed in E.

During Sepsis and COVID-19, the Pro-Inflammatory and Anti-Inflammatory Responses Are Concomitant.

The most severe forms of COVID-19 share many features with bacterial sepsis and have thus been considered to be a viral sepsis. Innate immunity and inflammation are closely linked. While the immune response aims to get rid of the infectious agent, the pro-inflammatory host response can result in organ injury including acute respiratory distress syndrome.

SEVERE CORONAVIRUS DISEASE 2019: FROM PATHOGENESIS TO THERAPY.

The COVID-19 pandemic has been a challenge to propose efficient therapies. Because severe SARS-CoV2 infection is a viral sepsis eventually followed by an immunological autoinflammatory phenomenon, many approaches have been inspired by the previous attempts made in bacterial sepsis, while specific antiviral strategies (use of interferon or specific drugs) have been additionally investigated. We summarize our current thinking on the use of SARS-CoV-2 antivirals, corticosteroids, anti-IL-1, anti-IL-6, anti-C5a, as well as stem cell therapy in severe COVID-19.

From Bacterial Poisons to Toxins: The Early Works of Pasteurians.

We review some of the precursor works of the Pasteurians in the field of bacterial toxins. The word "toxin" was coined in 1888 by Ludwig Brieger to qualify different types of poison released by bacteria. Pasteur had identified the bacteria as the cause of putrefaction but never used the word toxin.

Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: A secondary analysis of the CAPTAIN prospective multicenter cohort study.

Background: Although sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to identify subgroups with similar immune profiles and their clinical and outcome correlates.

Methods: A secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis.

Louis Pasteur: Between Myth and Reality.

Louis Pasteur is the most internationally known French scientist. He discovered molecular chirality, and he contributed to the understanding of the process of fermentation, helping brewers and winemakers to improve their beverages. He proposed a process, known as pasteurization, for the sterilization of wines.

Revisiting Metchnikoff's work in light of the COVID-19 pandemic.

Revisiting Metchnikoff's work in light of the COVID-19 pandemic illustrates how much this amazing scientist was a polymath, and one could speculate how much he would have been fascinated and most interested in following the course of the pandemic. Since he coined the word "gerontology", he would have been intrigued by the high mortality among the elderly, and by the concepts of immunosenescence and inflammaging that characterize the SARS-CoV-2 infection. While Metchnikoff's work is mainly associated with the discovery of the phagocytes and the birth of cellular innate immunity, he regularly invited his closest collaborators to investigate humoral immunity, and it was in his laboratory that Jules Bordet made his major discovery of the complement system.

COVID-19 and earlier pandemics, sepsis, and vaccines: A historical perspective.

Humanity has regularly faced the threat of epidemics and pandemics over the course of history. Successful attempts to protect populations were initially made with the development of new vaccines, such as those against plague and cholera, under the leadership of the bacteriologist Waldemar Haffkine. Vaccines have led to a complete eradication of smallpox and bovine plague and a major reduction in other infectious diseases including diphtheria, typhoid fever, poliomyelitis, and Haemophilus influenzae type B meningitis.

The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity.

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also affected, and acute disease is often followed by protracted complications.

Once upon a time, inflammation.

Inflammation has accompanied humans since their first ancestors appeared on Earth. Aulus Cornelius Celsus (25 BC-50 AD), a Roman encyclopedist, offered a still valid statement about inflammation: "", defining the four cardinal signs of inflammation as redness and swelling with heat and pain. While inflammation has long been considered as a morbid phenomenon, John Hunter (18 century) and Elie Metchnikoff (19 century) understood that it was a natural and beneficial event that aims to address a sterile or an infectious insult.

Bridging animal and clinical research during SARS-CoV-2 pandemic: A new-old challenge.

Many milestones in medical history rest on animal modeling of human diseases. The SARS-CoV-2 pandemic has evoked a tremendous investigative effort primarily centered on clinical studies. However, several animal SARS-CoV-2/COVID-19 models have been developed and pre-clinical findings aimed at supporting clinical evidence rapidly emerge.

[Jules Bordet, a man of conviction. Centenary of his Nobel Prize].

Jules Bordet came to the Institut Pasteur soon after his MD graduation at the Université libre de Bruxelles, thanks to a grant from the Belgian government. He joined there the laboratory of Elie Metchnikoff, the father of phagocytes and cellular immunity. Amazingly, he will decipher there some of the key mechanisms of humoral immunity initially discovered by the German school against which his mentor was fighting.

SARS-CoV-2/COVID-19: Evolving Reality, Global Response, Knowledge Gaps, and Opportunities.

Approximately 3 billion people around the world have gone into some form of social separation to mitigate the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The uncontrolled influx of patients in need of emergency care has rapidly brought several national health systems to near-collapse with deadly consequences to those afflicted by Coronavirus Disease 2019 (COVID-19) and other critical diseases associated with COVID-19. Solid scientific evidence regarding SARS-CoV-2/COVID-19 remains scarce; there is an urgent need to expand our understanding of the SARS-CoV-2 pathophysiology to facilitate precise and targeted treatments.

Sepsis therapies: learning from 30 years of failure of translational research to propose new leads.

Sepsis has been identified by the World Health Organization (WHO) as a global health priority. There has been a tremendous effort to decipher underlying mechanisms responsible for organ failure and death, and to develop new treatments. Despite saving thousands of animals over the last three decades in multiple preclinical studies, no new effective drug has emerged that has clearly improved patient outcomes.

H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation.

Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation is unknown. Here we show that following LPS-induced endotoxemia in mice, NK cells acquire cell-intrinsic memory-like properties, showing increased production of IFNγ upon specific secondary stimulation.

André Boivin: A pioneer in endotoxin research and an amazing visionary during the birth of molecular biology.

André Boivin (1895–1949) started his career in Marseille as a biochemist. Soon after the discovery of insulin, he worked on its purification, allowing for the treatment of local patients. He later moved to Strasbourg and set-up a microtitration technique of small carbon molecules and a method for quantifying purine and pyrimidine bases.

100th Anniversary of Jules Bordet's Nobel Prize: Tribute to a Founding Father of Immunology.

The 100th Anniversary of the Nobel Prize in Physiology or Medicine 1919 awarded to Jules Bordet offers the opportunity to underline the contributions of this Belgian doctor to the blooming of immunology at the end of the nineteenth century at the Institut Pasteur de Paris. It is also the occasion to emphasize his achievements as director of the Institut Pasteur du Brabant and professor at the Université libre de Bruxelles. Both in France and Belgium, he developed a holistic vision of immunology as a science at the crossroads of chemistry, physiology, and microbiology.

Duclaux, Chamberland, Roux, Grancher, and Metchnikoff: the five musketeers of Louis Pasteur.

The Institut Pasteur was created thanks to worldwide generosity with the aim to welcome and treat rabies patients, to provide a place for scientific research and to offer new teaching programs in microbiology. Louis Pasteur invited his main collaborators, who had accompanied him during his previous investigations at École Normale Supérieure, to join him in his new institute. They contributed to the principle discoveries of Pasteur, such as the fight against spontaneous generation, the identification of the ferments of putrefaction, the fight against the silk worm disease, the research on wine and beer, and the set-up of the first vaccines against avian cholera, anthrax, swine erysipelas and rabies.

From septicemia to sepsis 3.0 - from Ignaz Semmelweis to Louis Pasteur.

Sepsis remains a contemporary threat, and its frequency remains high amongst an aging population. Its definition has been regularly revisited, but the impact of the translational research studying it remains very modest compared to the results seen after the introduction of hygiene and the use of antibiotics. In the past, the main forms of sepsis were hospital gangrene (also known as nosocomial fever or putrid fever) that affected the wounded, and puerperal fever that affected women shortly after delivery.