RESUMEN

Trained innate immunity can be induced in human macrophages by microbial ligands, but it is unknown if exposure to endogenous alarmins such as cathelicidins can have similar effects. Previously, we demonstrated sustained protection against infection by the chicken cathelicidin-2 analog DCATH-2. Thus, we assessed the capacity of cathelicidins to induce trained immunity. PMA-differentiated THP-1 (dTHP1) cells were trained with cathelicidin analogs for 24 hours and restimulated after a 3-day rest period. DCATH-2 training of dTHP-1 cells amplified their proinflammatory cytokine response when restimulated with TLR2/4 agonists. Trained cells displayed a biased cellular metabolism towards mTOR-dependent aerobic glycolysis and long-chain fatty acid accumulation and augmented microbicidal activity. DCATH-2-induced trained immunity was inhibited by histone acetylase inhibitors, suggesting epigenetic regulation, and depended on caveolae/lipid raft-mediated uptake, MAPK p38 and purinergic signaling. To our knowledge, this is the first report of trained immunity by host defense peptides.

Asunto(s)

Epigénesis Genética , Péptidos Catiónicos Antimicrobianos/metabolismo , Catelicidinas/farmacología , Humanos , Inmunidad Innata , Macrófagos

RESUMEN

Shigella spp. and E. coli are closely related and cannot be distinguished using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) with commercially available databases. Here, three alternative approaches using MALDI-TOF MS to identify and distinguish Shigella spp., E. coli, and its pathotype EIEC were explored and evaluated using spectra of 456 Shigella spp., 42 E. coli, and 61 EIEC isolates. Identification with a custom-made database resulted in >94% Shigella identified at the genus level and >91% S. sonnei and S. flexneri at the species level, but the distinction of S. dysenteriae, S. boydii, and E. coli was poor. With biomarker assignment, 98% S. sonnei isolates were correctly identified, although specificity was low. Discriminating markers for S. dysenteriae, S. boydii, and E. coli were not assigned at all. Classification models using machine learning correctly identified Shigella in 96% of isolates, but most E. coli isolates were also assigned to Shigella. None of the proposed alternative approaches were suitable for clinical diagnostics for identifying Shigella spp., E. coli, and EIEC, reflecting their relatedness and taxonomical classification. We suggest the use of MALDI-TOF MS for the identification of the Shigella spp./E. coli complex, but other tests should be used for distinction.

RESUMEN

Based on the theory of social change, cultural evolution, and human development, we propose a mechanism whereby increased danger in society causes predictable shifts in valued forms of intelligence: 1. Practical intelligence rises in value relative to abstract intelligence; and 2. social intelligence shifts from measuring how well individuals can negotiate the social world to achieve their personal aims to measuring how well they can do so to achieve group aims. We document these shifts during the COVID-19 pandemic and argue that they led to an increase in the size and strength of social movements.

RESUMEN

What is the effect of a life-threatening pandemic at the societal level? An expanded Theory of Social Change, Cultural Evolution, and Human Development predicts that, during a period of increasing survival threat and decreasing prosperity, humans will shift toward the psychology and behavior typical of the small-scale, collectivistic, and rural subsistence ecologies in which we evolved. In particular, subjective mortality salience, engagement in subsistence activities, and collectivism will all increase, while the aspiration to be wealthy will decrease. Because coronavirus has forced unprecedented proportions of human activity online, we tested hypotheses derived from the theory by analyzing big data samples for 70 days before and 70 days after the coronavirus pandemic stimulated President Trump to declare a national emergency. Google searches were used for an exploratory study; the exploratory study was followed by three independent replications on Twitter, internet forums, and blogs. Across all four internet platforms, terms related to subjective mortality salience, engagement in subsistence activities, and collectivism showed massive increases. These findings, coupled with prior research testing this theory, indicate that humans may have an evolutionarily conditioned response to the level of death and availability of material resources in society. More specifically, humans may shift their behavior and psychology toward that found in subsistence ecologies under conditions of high mortality and low prosperity or, conversely, toward behavior and psychology found in modern commercial ecologies under conditions of low mortality and high prosperity.