7 research outputs found
Glucose metabolism and its role in the maturation and migration of human CD1c+ dendritic cells following exposure to BCG
IntroductionTuberculosis (TB) still kills over 1 million people annually. The only approved vaccine, BCG, prevents disseminated disease in children but shows low efficacy at preventing pulmonary TB. Myeloid dendritic cells (mDCs) are promising targets for vaccines and immunotherapies to combat infectious diseases due to their essential role in linking innate and adaptive immune responses. DCs undergo metabolic reprogramming following exposure to TLR agonists, which is thought to be a prerequisite for a successful host response to infection. We hypothesized that metabolic rewiring also plays a vital role in the maturation and migration of DCs stimulated with BCG. Consequently, we investigated the role of glycolysis in the activation of primary human myeloid CD1c+ DCs in response to BCG. Methods/resultsWe show that CD1c+ mDC mature and acquire a more energetic phenotype upon challenge with BCG. Pharmacological inhibition of glycolysis with 2-deoxy-D-glucose (2-DG) decreased cytokine secretion and altered cell surface expression of both CD40 and CCR7 on BCG-challenged, compared to untreated, mDCs. Furthermore, inhibition of glycolysis had differential effects on infected and uninfected bystander mDCs in BCG-challenged cultures. For example, CCR7 expression was increased by 2-DG treatment following challenge with BCG and this increase in expression was seen only in BCG-infected mDCs. Moreover, although 2-DG treatment inhibited CCR7-mediated migration of bystander CD1C+ DCs in a transwell assay, migration of BCG-infected cells proceeded independently of glycolysis. DiscussionOur results provide the first evidence that glycolysis plays divergent roles in the maturation and migration of human CD1c+ mDC exposed to BCG, segregating with infection status. Further investigation of cellular metabolism in DC subsets will be required to determine whether glycolysis can be targeted to elicit better protective immunity against Mtb
To which world regions does the valence–dominance model of social perception apply?
Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of
how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social
judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether
these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across
11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy,
the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated
dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance
model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed
when we use different extraction methods and correlate and rotate the dimension reduction solution.C.L. was supported by the Vienna Science and Technology Fund (WWTF VRG13-007);
L.M.D. was supported by ERC 647910 (KINSHIP); D.I.B. and N.I. received funding from
CONICET, Argentina; L.K., F.K. and Á. Putz were supported by the European Social
Fund (EFOP-3.6.1.-16-2016-00004; ‘Comprehensive Development for Implementing
Smart Specialization Strategies at the University of Pécs’). K.U. and E. Vergauwe were
supported by a grant from the Swiss National Science Foundation (PZ00P1_154911 to E.
Vergauwe). T.G. is supported by the Social Sciences and Humanities Research Council
of Canada (SSHRC). M.A.V. was supported by grants 2016-T1/SOC-1395 (Comunidad
de Madrid) and PSI2017-85159-P (AEI/FEDER UE). K.B. was supported by a grant
from the National Science Centre, Poland (number 2015/19/D/HS6/00641). J. Bonick
and J.W.L. were supported by the Joep Lange Institute. G.B. was supported by the Slovak
Research and Development Agency (APVV-17-0418). H.I.J. and E.S. were supported
by a French National Research Agency ‘Investissements d’Avenir’ programme grant
(ANR-15-IDEX-02). T.D.G. was supported by an Australian Government Research
Training Program Scholarship. The Raipur Group is thankful to: (1) the University
Grants Commission, New Delhi, India for the research grants received through its
SAP-DRS (Phase-III) scheme sanctioned to the School of Studies in Life Science;
and (2) the Center for Translational Chronobiology at the School of Studies in Life
Science, PRSU, Raipur, India for providing logistical support. K. Ask was supported by
a small grant from the Department of Psychology, University of Gothenburg. Y.Q. was
supported by grants from the Beijing Natural Science Foundation (5184035) and CAS
Key Laboratory of Behavioral Science, Institute of Psychology. N.A.C. was supported
by the National Science Foundation Graduate Research Fellowship (R010138018). We
acknowledge the following research assistants: J. Muriithi and J. Ngugi (United States
International University Africa); E. Adamo, D. Cafaro, V. Ciambrone, F. Dolce and E.
Tolomeo (Magna Græcia University of Catanzaro); E. De Stefano (University of Padova);
S. A. Escobar Abadia (University of Lincoln); L. E. Grimstad (Norwegian School of
Economics (NHH)); L. C. Zamora (Franklin and Marshall College); R. E. Liang and R.
C. Lo (Universiti Tunku Abdul Rahman); A. Short and L. Allen (Massey University, New
Zealand), A. Ateş, E. Güneş and S. Can Özdemir (Boğaziçi University); I. Pedersen and T.
Roos (Åbo Akademi University); N. Paetz (Escuela de Comunicación Mónica Herrera);
J. Green (University of Gothenburg); M. Krainz (University of Vienna, Austria); and B.
Todorova (University of Vienna, Austria). The funders had no role in study design, data
collection and analysis, decision to publish or preparation of the manuscript.https://www.nature.com/nathumbehav/am2023BiochemistryGeneticsMicrobiology and Plant Patholog
A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.
The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world
The Iron Chelator Desferrioxamine Increases the Efficacy of Bedaquiline in Primary Human Macrophages Infected with BCG
For over 50 years, patients with drug-sensitive and drug-resistant tuberculosis have undergone long, arduous, and complex treatment processes with several antimicrobials. With the prevalence of drug-resistant strains on the rise and new therapies for tuberculosis urgently required, we assessed whether manipulating iron levels in macrophages infected with mycobacteria offered some insight into improving current antimicrobials that are used to treat drug-resistant tuberculosis. We investigated if the iron chelator, desferrioxamine, can support the function of human macrophages treated with an array of second-line antimicrobials, including moxifloxacin, bedaquiline, amikacin, clofazimine, linezolid and cycloserine. Primary human monocyte-derived macrophages were infected with Bacillus Calmette-Guérin (BCG), which is pyrazinamide-resistant, and concomitantly treated for 5 days with desferrioxamine in combination with each one of the second-line tuberculosis antimicrobials. Our data indicate that desferrioxamine used as an adjunctive treatment to bedaquiline significantly reduced the bacterial load in human macrophages infected with BCG. Our findings also reveal a link between enhanced bactericidal activity and increases in specific cytokines, as the addition of desferrioxamine increased levels of IFN-γ, IL-6, and IL-1β in BCG-infected human monocyte-derived macrophages (hMDMs) treated with bedaquiline. These results provide insight, and an in vitro proof-of-concept, that iron chelators may prove an effective adjunctive therapy in combination with current tuberculosis antimicrobials
To which world regions does the valence-dominance model of social perception apply?
Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy, the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution
To Which World Regions Does the Valence-Dominance Model of Social Perception Apply?
Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy, the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution
To Which World Regions Does the Valence-Dominance Model of Social Perception Apply?
Over the past 10 years, Oosterhof and Todorov’s valence–dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov’s methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov’s original analysis strategy, the valence–dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence–dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution