From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation

Studies on monocyte and macrophage biology and differentiation have revealed the pleiotropic activities of these cells. Macrophages are tissue sentinels that maintain tissue integrity by eliminating/repairing damaged cells and matrices. In this M2-like mode they can also promote tumor growth. Conversely, M1-like macrophages are key effector cells for the elimination of pathogens, virally infected, and cancer cells. Macrophage differentiation from monocytes occurs in the tissue in concomitance with the acquisition of a functional phenotype that depends on microenvironmental signals, thereby accounting for the many and apparently opposed macrophage functions. Many questions arise. When monocytes differentiate into macrophages in a tissue (concomitantly adopting a specific functional program, M1 or M2), do they all die during the inflammatory reaction, or do some of them survive? Do those that survive become quiescent tissue macrophages, able to react as naïve cells to a new challenge? Or, do monocyte-derived tissue macrophages conserve a memory of their past inflammatory activation? This review will address some of these important questions under the general framework of the role of monocytes and macrophages in the initiation, development, resolution and chronicization of inflammation

The SARS-CoV-2 Nucleoprotein Induces Innate Memory in Human Monocytes

The interaction of SARS-CoV-2 with the human immune system is at the basis of the positive or negative outcome of the infection. Monocytes and macrophages, which are major innate immune/inflammatory effector cells, are not directly infected by SARS-CoV-2, however they can react to the virus and mount a strong reaction. Whether this first interaction and reaction may bias innate reactivity to re-challenge, a phenomenon known as innate memory, is currently unexplored and may be part of the long-term sequelae of COVID-19. Here, we have tested the capacity of SARS-CoV-2 and some of its proteins to induce innate memory in human monocytes in vitro. Our preliminary results show that the Spike protein subunits S1 and S2 and the entire heat-inactivated virus have no substantial effect. Conversely, monocytes pre-exposed to the nucleocapsid N protein react to subsequent viral or bacterial challenges with an increased production of anti-inflammatory IL-1Ra, a response profile suggesting a milder response to new infections

100 Years of BCG Immunization: Past, Present, and Future

The 100th anniversary of the introduction of Bacille–Calmette–Guérin (BCG) as a tuberculosis (TB) vaccine is an occasion warranting further investigation of the early attempts which culminated in the introduction of BCG as a TB vaccine, as well as of subsequent recognition of failures, new findings that broaden its applications, outstanding questions, and approaches towards the development of novel vaccine candidates [...

Criatividade e Tecnologias na Educação Musical

A presente pesquisa ressalta a inclusão de objetos comuns junto a programas virtuais, no ensino de música para crianças, propondo laboratórios de criatividade e novas formas de se ouvir e perceber música. A pretensão é identificar a importância de realizar práticas criativas a nível de sons naturais e digitais; também pretende-se refletir sobre metodologias do ensino de música e direcionar propostas de estudos deste mesmo contexto para diferentes faixas etárias, de forma a propor um processo educacional que se inicia em práticas simples e vão ganhando consistência com o decorrer do aprofundamento das etapas. Este estudo foi motivado pelo facto de que essas possibilidades musicais, que multiplicam incalculavelmente a quantidade de resultados sonoros, ainda são pouco exploradas, no ambiente escolar. Os objetivos aqui delineados são relativos a prática e o entendimento dos elementos da música. As crianças são orientadas a um trabalho de exercícios criativos, com exploração sonora, simultaneamente, com a leitura, a manipulação de programas digitais e a composição. O trabalho recebeu uma metodologia qualitativa, onde profissionais da educação musical, de diferentes países, foram entrevistados para comparação de respostas. Foi observado também em quais contextos os professores utilizam ferramentas empíricas: se apenas para suprir a falta de infraestrutura das escolas, ou se para fundamentar uma filosofia e um olhar científico para a música e para as práticas musicais. Os resultados mostram que os alunos que são expostos a tais práticas criativas possuem uma perspetiva mais calculista e complexa perante a música, em relação aos alunos que não são expostos a tais exercícios, além de que são capazes de desenvolver narrativas mais interessantes a nível musical.This research highlights the inclusion of common objects with virtual programs, in teaching music to children, proposing creativity laboratories and new ways of listening to and understanding music. The intention is to identify the importance of performing creative practices in terms of natural and digital sounds; It is also intended to reflect on music teaching methodologies and direct proposals for studies in this same context for different age groups, in order to propose an educational process that begins with simple practices and gains consistency as the steps progress. This study was motivated by the fact that these musical possibilities, which incalculably multiply the amount of sound results, are still little explored in the school environment. The goals outlined here are related to practice and understanding of the elements of music. Children are guided to a work of creative exercises, with sound exploration, simultaneously with reading, manipulation of digital programs and composition. The work received a qualitative methodology, where music education professionals from different countries were interviewed to compare answers. It was also observed in which contexts teachers use empirical tools: whether only to make up for the lack of infrastructure in schools, or whether to support a philosophy and a scientific look at music and musical practices. The results show that students who are exposed to such creative practices have a more calculating and complex perspective on music than students who are not exposed to such exercises, in addition to being able to develop more interesting narratives at a musical level

ALFABETIZAÇÃO E LETRAMENTO EM CRIANÇAS COM DEFICIÊNCIA INTELECTUAL

O presente artigo tem como tema o papel e a aprendizagem da leitura e da escrita para o desenvolvimento humano como prática social, considerando a condição indispensável de se saber ler e escrever como exercício de cidadania. Tem como objetivo refletir sobre a ocorrência dos processos de alfabetização e de letramento em crianças com deficiência intelectual. O estudo foi realizado por meio de pesquisa bibliográfica, pautando-se em uma abordagem qualitativa de pesquisa. As reflexões feitas ao longo da investigação trouxeram algumas considerações sobre a deficiência intelectual, caracterizando-a. Possibilitaram alguns apontamentos sobre os processos de alfabetização e de letramento. Como resultados da pesquisa, algumas reflexões foram possíveis acerca da ocorrência da alfabetização e do letramento em crianças com deficiência intelectual, discutindo como esses processos podem se dar por meio de práticas pedagógicas em salas de aula comum do ensino regular, contribuindo com a apropriação do mundo letrado e a inserção ativa dessa criança na sociedade

Mucosal delivery of anti-inflammatory IL-1Ra by sporulating recombinant bacteria

BACKGROUND: Mucosal delivery of therapeutic protein drugs or vaccines is actively investigated, in order to improve bioavailability and avoid side effects associated with systemic administration. Orally administered bacteria, engineered to produce anti-inflammatory cytokines (IL-10, IL-1Ra), have shown localised ameliorating effects in inflammatory gastro-intestinal conditions. However, the possible systemic effects of mucosally delivered recombinant bacteria have not been investigated. RESULTS: B. subtilis was engineered to produce the mature human IL-1 receptor antagonist (IL-1Ra). When recombinant B. subtilis was instilled in the distal colon of rats or rabbits, human IL-1Ra was found both in the intestinal lavage and in the serum of treated animals. The IL-1Ra protein in serum was intact and biologically active. IL-1-induced fever, neutrophilia, hypoglycemia and hypoferremia were inhibited in a dose-dependent fashion by intra-colon administration of IL-1Ra-producing B. subtilis. In the mouse, intra-peritoneal treatment with recombinant B. subtilis could inhibit endotoxin-induced shock and death. Instillation in the rabbit colon of another recombinant B. subtilis strain, which releases bioactive human recombinant IL-1β upon autolysis, could induce fever and eventually death, similarly to parenteral administration of high doses of IL-1β. CONCLUSIONS: A novel system of controlled release of pharmacologically active proteins is described, which exploits bacterial autolysis in a non-permissive environment. Mucosal administration of recombinant B. subtilis causes the release of cytoplasmic recombinant proteins, which can then be found in serum and exert their biological activity in vivo systemically

Impact of engineered nanoparticles in initiating or modulating pathology-related Inflammation

The possibility that nanomaterials could perturb the normal course of an inflammatory response is a key issue when assessing nano-immunosafety. The alteration of the normal progress of an inflammatory response may have pathological consequences, since inflammation is a major defensive mechanism and its efficiency maintains the body’s health. We can thus consider as pathology-related inflammation those inflammatory reactions that, instead of eliminating foreign agents, lack down-regulation and cause tissue damage. To assess the ability of nanoparticles to initiate and modulate inflammatory reactions, an in vitro model was used that recapitulates all the stages of infection-induced inflammation, from initiation to resolution, based on human primary blood monoytes. A parallel model reproducing pathological chronic inflammation shows that the differences between resolving and persistent inflammation are subtle and evident only upon kinetic analysis of gene expression profiles and production of inflammatory factors. Rigorously endotoxin-free Au and Ag nanoparticles have been assessed for their ability to directly initiate in vitro inflammation and for their capacity to modulate the course both physiological resolving inflammation and pathological persistent inflammation. In no case significant effects were observed, with the exception of a transient increase of the inflammatory response in the presence of Ag nanoparticles. An important issue in the regulation of monocyte/macrophage inflammatory functions is the capacity of innate “memory”, i.e., the ability of respond differently to a challenge if previously primed with the same or a different agent. How nanoparticles can impact innate memory was assessed by using Au nanoparticles as priming and challenge agent with and without LPS and zymosan. Priming with LPS and zymosan could drastically decrease the response of monocytes (production of TNFa) to a challenge with any stimulus, given 7 days after the first. The presence of Au nanoparticles did not influence such behaviour. Likewise, Au nanoparticles did not directly induce memory, i.e., did not influence the response of monocytes to subsequent stimuli. We conclude that Au and Ag nanoparticles, at the size and concentrations used, are taken up by monocytes without this causing any notable interference with their capacity to mount an adequate defensive responses to microbial challenges, either immediate or after some time from exposure. This work was supported by per EU FP7 projects HUMUNITY and BioCog, the H2020 project PANDORA, the CNR Flagship Project InterOmics, and the cluster project Medintech of the Italian Ministry of Education, University and Research