Role of Innate Immunity in the Pathogenesis of Chronic Rhinosinusitis: Progress and New Avenues

Chronic rhinosinusitis is a heterogeneous and multifactorial disease with unknown etiology. Aberrant responses to microorganisms have been suggested to play a role in the pathophysiology of the disease. Research has focused on the presence, detection, response to, and eradication of these potential threats. Main topics seem to center on the contribution of structural cells such as epithelium and fibroblasts, on the consequences of activation of pattern-recognition receptors, and on the role of antimicrobial agents. This research should be viewed not only in the light of a comparison between healthy and diseased individuals, but also in a comparison between patients who do or do not respond to treatment. New players that could play a role in the pathophysiology seem to surface at regular intervals, adding to our understanding (and the complexity) of the disease and opening new avenues that may help fight this incapacitating disease

Warmth and competence perceptions of key protagonists are associated with containment measures during the COVID-19 pandemic: Evidence from 35 countries

It is crucial to understand why people comply with measures to contain viruses and their effects during pandemics. We provide evidence from 35 countries (Ntotal = 12,553) from 6 continents during the COVID-19 pandemic (between 2021 and 2022) obtained via cross-sectional surveys that the social perception of key protagonists on two basic dimensions—warmth and competence—plays a crucial role in shaping pandemic-related behaviors. Firstly, when asked in an open question format, heads of state, physicians, and protest movements were universally identified as key protagonists across countries. Secondly, multiple-group confirmatory factor analyses revealed that warmth and competence perceptions of these and other protagonists differed significantly within and between countries. Thirdly, internal meta-analyses showed that warmth and competence perceptions of heads of state, physicians, and protest movements were associated with support and opposition intentions, containment and prevention behaviors, as well as vaccination uptake. Our results have important implications for designing effective interventions to motivate desirable health outcomes and coping with future health crises and other global challenges.publishedVersio

Prohibitin: A novel regulator of inflammatory cell dynamics

Inflammation is a complex mechanism primarily driven by the immune system to eradicate pathogens/foreign substances and restore tissue homeostasis. Despite the beneficial effects that inflammation employs, signaling can often become dysregulated leading to uncontrolled systemic inflammation and irreversible host tissue damage. Therefore, regulating the cellular and physiological mechanisms of inflammation constitutes a viable avenue of research to mitigate inflammatory disease progression. Herein, we evaluated prohibitins (PHB1 and PHB2), pleiotropic homologous proteins with known anti-inflammatory and antioxidant capabilities, in the context of systemic inflammation as well as macrophage-specific inflammatory signaling. Using two in vivo models of systemic inflammation, we found that PHB1 levels were increased in serum, suggesting a potential signaling role for PHB. Moreover, recombinant PHB1 treatment mitigated systemic inflammation and tissue/organ injury and modulated the phenotype of circulating immune cells. When investigating the role of PHB specifically in monocytes/macrophages, we found that PHB not only increased populations of pro-inflammatory monocytes in vivo but also regulated vital macrophage inflammatory signaling (as shown in vitro). We determined that PHB is a scaffold protein important for macrophage lipid raft formation and subsequent receptor trafficking. PHB modulation of macrophages influenced cell surface display of lipid-raft-dependent receptors and downstream inflammatory signaling cascades. To our knowledge, these are the first data to reveal PHB's pro-inflammatory effects in macrophages and its mechanistic operation of lipid-raft-dependent signal transduction in macrophages. In this report, we provide insight into the diverse yet complementary roles of PHB in regulating various aspects of immune-driven inflammatory processes

Prohibitin: A novel regulator of inflammatory cell dynamics

Inflammation is a complex mechanism primarily driven by the immune system to eradicate pathogens/foreign substances and restore tissue homeostasis. Despite the beneficial effects that inflammation employs, signaling can often become dysregulated leading to uncontrolled systemic inflammation and irreversible host tissue damage. Therefore, regulating the cellular and physiological mechanisms of inflammation constitutes a viable avenue of research to mitigate inflammatory disease progression. Herein, we evaluated prohibitins (PHB1 and PHB2), pleiotropic homologous proteins with known anti-inflammatory and antioxidant capabilities, in the context of systemic inflammation as well as macrophage-specific inflammatory signaling. Using two in vivo models of systemic inflammation, we found that PHB1 levels were increased in serum, suggesting a potential signaling role for PHB. Moreover, recombinant PHB1 treatment mitigated systemic inflammation and tissue/organ injury and modulated the phenotype of circulating immune cells. When investigating the role of PHB specifically in monocytes/macrophages, we found that PHB not only increased populations of pro-inflammatory monocytes in vivo but also regulated vital macrophage inflammatory signaling (as shown in vitro). We determined that PHB is a scaffold protein important for macrophage lipid raft formation and subsequent receptor trafficking. PHB modulation of macrophages influenced cell surface display of lipid-raft-dependent receptors and downstream inflammatory signaling cascades. To our knowledge, these are the first data to reveal PHB's pro-inflammatory effects in macrophages and its mechanistic operation of lipid-raft-dependent signal transduction in macrophages. In this report, we provide insight into the diverse yet complementary roles of PHB in regulating various aspects of immune-driven inflammatory processes

Prohibitin-1 Is a Dynamically Regulated Blood Protein With Cardioprotective Effects in Sepsis.

Background In sepsis, circulating cytokines and lipopolysaccharide elicit mitochondrial dysfunction and cardiomyopathy, a major cause of morbidity and mortality with this condition. Emerging research places the PHB1 (lipid raft protein prohibitin-1) at the nexus of inflammation, metabolism, and oxidative stress. PHB1 has also been reported in circulation, though its function in this compartment is completely unknown. Methods and Results Using a wide-ranging approach across multiple in vitro and in vivo models, we interrogated the functional role of intracellular and circulating PHB1 in the heart during sepsis, and elucidated some of the mechanisms involved. Upon endotoxin challenge or sepsis induction in rodent models, PHB1 translocates from mitochondria to nucleus in cardiomyocytes and is secreted into the circulation from the liver in a manner dependent on nuclear factor (erythroid-derived 2)-like 2, a key transcriptional regulator of the antioxidant response. Overexpression or treatment with recombinant human PHB1 enhances the antioxidant/anti-inflammatory response and protects HL-1 cardiomyocytes from mitochondrial dysfunction and toxicity from cytokine stress. Importantly, administration of recombinant human PHB1 blunted inflammation and restored cardiac contractility and ATP production in mice following lipopolysaccharide challenge. This cardioprotective, anti-inflammatory effect of recombinant human PHB1 was determined to be independent of nuclear factor (erythroid-derived 2)-like 2, but partially dependent on PI3K/AKT  signaling in the heart. Conclusions These findings reveal a previously unknown cardioprotective effect of PHB1 during sepsis, and illustrate a pro-survival, protective role for PHB1 in the circulation. Exploitation of circulating PHB1 as a biomarker and/or therapeutic could have widespread benefit in the clinical management of sepsis and other severe inflammatory disorders

Preschool children’s conversational skills for explaining game rules: communicative guidance strategies as a function of type of relationship and gender

International audienceTen trios of children from 4 to 6 years old were observed in a situation where one child (the expert) who had learned the rules of a game explained these rules to two other children at the same time (the novices): one with whom s/he had a positive relationship and the other with whom her/his relationship was negative. Within this asymmetrical situation created artificially, the children functioned on the basis of a complex tutorial contract. The results indicated that, at these young ages, children are capable to strongly manage three dimensions of the explanatory goal: interactional, ideational (management of the object), and linguistic. However, the errors made by the novices were regulated differently, depending on the type of relationship and gender: the experts in boy trios intervened less frequently when errors were made by the novice with whom the relationship was negative (i.e., the not-friend novice) than with the other novice; conversely, the experts in girl trios intervened less frequently when errors were produced by the novice with whom the relationship was positive (i.e., the friend novice) than with the other novice. An analysis of the communicative strategies observed here highlights early sophisticated pragmatic skills in this interactive assigned design