Secretory immunoglobulin A (SIgA) enhances host-microbiota symbiosis, whereas SIgM remains poorly understood. We found that gut IgM+ plasma cells (PCs) were more abundant in humans than mice and ...clonally related to a large repertoire of memory IgM+ B cells disseminated throughout the intestine but rare in systemic lymphoid organs. In addition to sharing a gut-specific gene signature with memory IgA+ B cells, memory IgM+ B cells were related to some IgA+ clonotypes and switched to IgA in response to T cell-independent or T cell-dependent signals. These signals induced abundant IgM which, together with SIgM from clonally affiliated PCs, recognized mucus-embedded commensals. Bacteria recognized by human SIgM were dually coated by SIgA and showed increased richness and diversity compared to IgA-only-coated or uncoated bacteria. Thus, SIgM may emerge from pre-existing memory rather than newly activated naive IgM+ B cells and could help SIgA to anchor highly diverse commensal communities to mucus.
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•IgM+ PCs generating SIgM are relatively abundant in human but not mouse gut•IgM+ PCs clonally relate to a large gut repertoire of memory IgM+ B cells•Gut memory IgM+ B cells express a tissue-specific signature and can switch to IgA•Human but not mouse SIgM binds a highly diverse microbiota dually coated by SIgA
Magri et al. found that the human gut includes a large memory IgM+ B cell repertoire clonally related to plasma cells mounting SIgM responses against mucus-embedded commensals co-targeted by SIgA. Dually coated bacteria are detected in humans but not mice and show increased diversity and richness compared to SIgA-only-coated or uncoated bacteria.
Mechanistic target of rapamycin (mTOR) enhances immunity in addition to orchestrating metabolism. Here we show that mTOR coordinates immunometabolic reconfiguration of marginal zone (MZ) B cells, a ...pre-activated lymphocyte subset that mounts antibody responses to T-cell-independent antigens through a Toll-like receptor (TLR)-amplified pathway involving transmembrane activator and CAML interactor (TACI). This receptor interacts with mTOR via the TLR adapter MyD88. The resulting mTOR activation instigates MZ B-cell proliferation, immunoglobulin G (IgG) class switching, and plasmablast differentiation through a rapamycin-sensitive pathway that integrates metabolic and antibody-inducing transcription programs, including NF-κB. Disruption of TACI-mTOR interaction by rapamycin, truncation of the MyD88-binding domain of TACI, or B-cell-conditional mTOR deficiency interrupts TACI signaling via NF-κB and cooperation with TLRs, thereby hampering IgG production to T-cell-independent antigens but not B-cell survival. Thus, mTOR drives innate-like antibody responses by linking proximal TACI signaling events with distal immunometabolic transcription programs.
B cells thwart antigenic aggressions by releasing immunoglobulin M (IgM), IgG, IgA, and IgE, which deploy well-understood effector functions. In contrast, the role of secreted IgD remains mysterious. ...We found that some B cells generated IgD-secreting plasma cells following early exposure to external soluble antigens such as food proteins. Secreted IgD targeted basophils by interacting with the CD44-binding protein galectin-9. When engaged by antigen, basophil-bound IgD increased basophil secretion of interleukin-4 (IL-4), IL-5, and IL-13, which facilitated the generation of T follicular helper type 2 cells expressing IL-4. These germinal center T cells enhanced IgG1 and IgE but not IgG2a and IgG2b responses to the antigen initially recognized by basophil-bound IgD. In addition, IgD ligation by antigen attenuated allergic basophil degranulation induced by IgE co-ligation. Thus, IgD may link B cells with basophils to optimize humoral T helper type 2-mediated immunity against common environmental soluble antigens.
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•IgD interacts with basophils through the CD44-binding protein galectin-9•IgD ligation by antigen elicits basophil release of Th2 cell-associated cytokines•IgD-activated basophils enhance B cell production of IgG1 and IgE•IgD interferes with IgE-mediated basophil degranulation
The function of IgD has been mysterious. Shan et al. find that IgD recognized food antigens and targeted basophils through galectin-9. IgD ligation by antigen induced basophil secretion of IL-4, IL-5, and IL-13, which amplified Th2 cell-mediated IgG1 and IgE production by B cells. IgD also constrained IgE-mediated basophil degranulation.
•A RBD-based synthetic peptide was shown safe when injected to mice and hamsters.•The vaccine candidate elicited antibodies that sustained for up to 2 months in mice.•Neutralizing antibodies and ...antigen-specific CD4 + CD8 + -IFNγ responses were detected.
The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions.
Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.
B cells thwart antigenic aggressions by releasing immunoglobulin M (IgM), IgG, IgA and IgE, which deploy well-understood effector functions. In contrast, the role of secreted IgD remains mysterious. ...We found that some B cells generated IgD-secreting plasma cells following early exposure to external soluble antigens such as food proteins. Secreted IgD targeted basophils by interacting with the CD44-binding protein galectin-9. When engaged by antigen, basophil-bound IgD incresed basophil secretion of interleukin-4 (IL-4), IL-5 and IL-13, which facilitated the generation of T follicular helper type-2 cells expressing IL-4. These germinal center T cells enhanced IgG1 and IgE but not IgG2a and IgG2b responses to the antigen initially recognized by basophil-bound IgD. In addition, IgD ligation by antigen attenuated allergic basophil degranulation induced by IgE co-ligation. Thus, IgD may link B cells with basophils to optimize humoral T helper type-2-mediated immunity against common environmental soluble antigens.
The function of IgD has been mysterious. Shan et al. find that IgD recognized food antigens and targeted basophils through galectin-9. IgD ligation by antigen induced basophil secretion of IL-4, IL-5 and IL-13, which amplified Th2 cell-mediated IgG1 and IgE production by B cells. IgD also constrained IgE-mediated basophil degranulation.
Es fundamental elaborar un protocolo de evaluación para garantizar rigor y homogeneidad en cualquier estudio de investigación.Asimismo, se requieren consideraciones específicas si la investigación se ...desarrolla en contexto educativo y en diferentes centroseducativos. Este trabajo tiene como objetivo describir el protocolo de evaluación del estudio de investigación titulado: Estudio PACO«Pedalea y Anda al COlegio». Además, se aportan recomendaciones globales y aplicaciones prácticas en el contexto educativo. El principalobjetivo del estudio PACO es fomentar el comportamiento de desplazamiento activo entre estudiantes de Educación Secundaria Obligatoriapara mejorar los niveles de actividad física y otros indicadores de salud asociados. Por ello, el protocolo de evaluación incluye lametodología e instrumentos específicos para evaluar en los adolescentes variables como: 1) modo de desplazamiento al centro educativoy otros factores psicosociales asociados a dicho desplazamiento mediante el cuestionario PACO alumnos, 2) barreras familiares para eldesplazamiento activo al centro educativo mediante el cuestionario PACO familias, 3) características antropométricas (peso, talla,perímetro de cintura y de cuello), 4) niveles de actividad física y gasto energético evaluados mediante acelererometría y 5) característicasde la ruta real casa-colegio registradas mediante Sistema de Posicionamiento Global. La transparencia en la metodología y logísticanecesaria para evaluar dichas variables en contexto educativo, es la clave para garantizar el rigor y la homogeneidad en futuras implementaciones,ya sean estas realizadas por investigadores o docentes. Finalmente, los datos obtenidos, serán fiables y relevantes para implementarestrategias educativas que fomenten la salud integral de los adolescentes.
It is essential to develop an evaluation protocol to develop rigor and homogeneity in any research study. Likewise, someconsiderations are specifically needed if the research is carried out in an educational context and in different schools. This work aims todescribe y the evaluation protocol of the research study entitled: PACO Study «Cycle and Walk to School». In addition, it provides globalrecommendations and practical applications in the educational context. The main objective of the PACO Study is to promote thebehaviour of active commuting among students of Compulsory Secondary Education to improve their physical activity levels and otherassociated health indicators. For this reason, the evaluation protocol includes the specific methodology and instruments for evaluatingvariables such as: 1) mode of commuting to school and other psychosocial factors associated with active commuting through the PACOstudent questionnaire, 2) family barriers to active commuting to school through the PACO families questionnaire, 3) anthropometriccharacteristics (weight, height, waist and neck circumference), 4) levels of physical activity and energy expenditure evaluated byaccelerometry and 5) characteristics of the real home-school route through a Global Positioning System. The transparency in themethodology and logistic necessary to evaluate the variables in the educational context is key to evaluate the rigor and homogeneity infuture implementations, whether they are carried out by researchers or teachers. Finally, the obtained data will be reliable and relevant toimplement educational strategies in order to promote an integral health of the adolescents.
The aim of this study was to examine the convergent validity of self-reported diary times for commuting to and from school with device-measured positional data (Global Positioning System; GPS) in ...Spanish adolescents.
Cross-sectional data were obtained from four Spanish public secondary schools in 2021, comprising 47 adolescents and 141 home-school and school-home trips. Participants self-reported the time they left and arrived at home and school through a commuting diary. They wore a GPS device recording the objective time during three trips (i.e., one home-school trip and two school-home trips). Agreement between commuting diary and GPS data regarding home-school trips and school-home trips was evaluated using Bland-Altman plots.
Total commuting time differed by 1 min (95% limits of agreement were 16.1 min and -18.1 min) between subjective and objective measures (adolescents reported 0.8 more minutes in home-school trips and 1 more minute in school-home trips compared to objective data). Passive commuters reported 0.7 more minutes and active commuters reported 1.2 more minutes in the total commuting time compared to objective data.
Self-reported commuting diaries may be a useful tool to obtain commuting times of adolescents in epidemiological research or when tools to measure objective times are not feasible.
This manuscript describes the rationale and protocol of a school-based randomized controlled trial called "Cycling and Walk to School" (PACO, by its Spanish acronym) that aims to promote cycling to ...and from school and physical activity (PA) in adolescents. This study will examine the effects of this intervention in cycling and active commuting to and from school (ACS), PA and several ACS-related factors based on self-determination theory (SDT) and a social-ecological model (SEM). A total of 360 adolescents attending six high schools (three experimental and three control) from three Spanish cities will participate in this randomized controlled trial. The intervention (four cycling sessions; 1-2 h per session, one session per week) will be conducted by the research staff; the control group will continue their usual activities. PA levels will be measured by accelerometers, whereas ACS and the other study variables will be self-reported using questionnaires at baseline and post-intervention. The primary outcomes will be: rates of cycling to school, ACS and PA levels. In addition, SDT-related variables and individual, interpersonal, community, and environment variables relevant to ACS will be based on SEM. The findings will provide a comprehensive understanding of the short-term effects of this school-based intervention on cycling to school behaviour, ACS and PA levels in Spanish adolescents.
Es fundamental elaborar un protocolo de evaluación para garantizar rigor y homogeneidad en cualquier estudio de investigación. Asimismo, se requieren consideraciones específicas si la investigación ...se desarrolla en contexto educativo y en diferentes centros educativos. Este trabajo tiene como objetivo describir el protocolo de evaluación del estudio de investigación titulado: Estudio PACO “Pedalea y Anda al Colegio”. Además, se aportan recomendaciones globales y aplicaciones prácticas en el contexto educativo. El principal objetivo del estudio PACO es fomentar el comportamiento de desplazamiento activo entre estudiantes de Educación Secundaria Obligatoria para mejorar los niveles de actividad física y otros indicadores de salud asociados. Por ello, el protocolo de evaluación incluye la metodología e instrumentos específicos para evaluar en los adolescentes variables como: 1) modo de desplazamiento al centro educativo y otros factores psicosociales asociados a dicho desplazamiento mediante el cuestionario PACO alumnos, 2) barreras familiares para el desplazamiento activo al centro educativo mediante el cuestionario PACO familias, 3) características antropométricas (peso, talla, perímetro de cintura y de cuello), 4) niveles de actividad física y gasto energético evaluados mediante acelererometría y 5) características de la ruta real casa-colegio registradas mediante Sistema de Posicionamiento Global. La transparencia en la metodología y logística necesaria para evaluar dichas variables en contexto educativo, es la clave para garantizar el rigor y la homogeneidad en futuras implementaciones, ya sean estas realizadas por investigadores o docentes. Finalmente, los datos obtenidos, serán fiables y relevantes para implementar estrategias educativas que fomenten la salud integral de los adolescentes.
Abstract. It is essential to develop an evaluation protocol to develop rigor and homogeneity in any research study. Likewise, some considerations are specifically needed if the research is carried out in an educational context and in different schools. This work aims to describe y the evaluation protocol of the research study entitled: PACO Study “Cycle and Walk to School”. In addition, it provides global recommendations and practical applications in the educational context. The main objective of the PACO Study is to promote the behaviour of active commuting among students of Compulsory Secondary Education to improve their physical activity levels and other associated health indicators. For this reason, the evaluation protocol includes the specific methodology and instruments for evaluating variables such as: 1) mode of commuting to school and other psychosocial factors associated with active commuting through the PACO student questionnaire, 2) family barriers to active commuting to school through the PACO families questionnaire, 3) anthropometric characteristics (weight, height, waist and neck circumference), 4) levels of physical activity and energy expenditure evaluated by accelerometry and 5) characteristics of the real home-school route through a Global Positioning System. The transparency in the methodology and logistic necessary to evaluate the variables in the educational context is key to evaluate the rigor and homogeneity in future implementations, whether they are carried out by researchers or teachers. Finally, the obtained data will be reliable and relevant to implement educational strategies in order to promote an integral health of the adolescents.
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