Inflammatory bowel disease (IBD) is a heterogeneous state of chronic intestinal inflammation of unknown cause encompassing Crohn’s disease (CD) and ulcerative colitis (UC). IBD has been linked to ...genetic and environmental factors, microbiota dysbiosis, exacerbated innate and adaptive immunity and epithelial intestinal barrier dysfunction. IBD is classically associated with gut accumulation of proinflammatory Th1 and Th17 cells accompanied by insufficient Treg numbers and Tr1 immune suppression. Inflammatory T cells guide innate cells to perpetuate a constant hypersensitivity to microbial antigens, tissue injury and chronic intestinal inflammation. Recent studies of intestinal mucosal homeostasis and IBD suggest involvement of innate lymphoid cells (ILCs). These lymphoid-origin cells are innate counterparts of T cells but lack the antigen receptors expressed on B and T cells. ILCs play important roles in the first line of antimicrobial defense and contribute to organ development, tissue protection and regeneration, and mucosal homeostasis by maintaining the balance between antipathogen immunity and commensal tolerance. Intestinal homeostasis requires strict regulation of the quantity and activity of local ILC subpopulations. Recent studies demonstrated that changes to ILCs during IBD contribute to disease development. A better understanding of ILC behavior in gastrointestinal homeostasis and inflammation will provide valuable insights into new approaches to IBD treatment. This review summarizes recent research into ILCs in intestinal homeostasis and the latest advances in the understanding of the role of ILCs in IBD, with particular emphasis on the interaction between microbiota and ILC populations and functions.
Inflammatory bowel disease (IBD) is an umbrella term for the chronic immune-mediated idiopathic inflammation of the gastrointestinal tract, manifesting as Crohn's disease (CD) or ulcerative colitis ...(UC). IBD is characterized by exacerbated innate and adaptive immunity in the gut in association with microbiota dysbiosis and the disruption of the intestinal barrier, resulting in increased bacterial exposure. In response to signals from microorganisms and damaged tissue, innate immune cells produce inflammatory cytokines and factors that stimulate T and B cells of the adaptive immune system, and a prominent characteristic of IBD patients is the accumulation of inflammatory T-cells and their proinflammatory-associated cytokines in intestinal tissue. Upon antigen recognition and activation, CD4 T-cells differentiate towards a range of distinct phenotypes: T helper(h)1, Th2, Th9, Th17, Th22, T follicular helper (Tfh), and several types of T-regulatory cells (Treg). T-cells are generated according to and adapt to microenvironmental conditions and participate in a complex network of interactions among other immune cells that modulate the further progression of IBD. This review examines the role of the CD4 T-cells most relevant to IBD, highlighting how these cells adapt to the environment and interact with other cell populations to promote or inhibit the development of IBD.
ABSTRACT
Atherosclerosis is a chronic disease characterized by vascular lipid retention and inflammation, and pattern recognition receptors (PRRs) are important contributors in early stages of the ...disease. Given the implication of the intracellular PRR nucleotide‐binding oligomerization domain 1 (NOD1) in cardiovascular diseases, we investigated its contribution to early atherosclerosis. We evidenced NOD1 induction in atherosclerotic human and mouse tissues, predominantly in vascular endothelial cells. Accordingly, NOD1 genetic inactivation in Apoe−/− mice reduced not only atherosclerosis burden, but also monocyte and neutrophil accumulation in atheromata. Of note, in the presence of either peptidoglycan or oxidized LDLs, endothelial NOD1 triggered VCAM‐1 up‐regulation through the RIP2‐NF‐κB axis in an autocrine manner, enhancing firm adhesion of both sets of myeloid cells to the inflamed micro‐ and macro vasculature in vivo. Our data define a major proatherogenic role for endothelial NOD1 in early leukocyte recruitment to the athero‐prone vasculature, thus introducing NOD1 as an innovative therapeutic target and potential prognostic molecule.—González‐Ramos, S., Paz‐García, M., Rius, C., del Monte‐Monge, A., Rodríguez, C., Fernández‐García, V., Andrés, V., Martínez‐González, J., Lasunción, M. A., Martín‐Sanz, P., Soehnlein, O., Boscá, L. Endothelial NOD1 directs myeloid cell recruitment in atherosclerosis through VCAM‐1. FASEB J. 33, 3912–3921 (2019). www.fasebj.org
Nuclear envelope lamin A/C proteins are a major component of the mammalian nuclear lamina, a dense fibrous protein meshwork located in the nuclear interior. Lamin A/C proteins regulate nuclear ...mechanics and structure and control cellular signaling, gene transcription, epigenetic regulation, cell cycle progression, cell differentiation, and cell migration. The immune system is composed of the innate and adaptive branches. Innate immunity is mediated by myeloid cells such as neutrophils, macrophages, and dendritic cells. These cells produce a rapid and nonspecific response through phagocytosis, cytokine production, and complement activation, as well as activating adaptive immunity. Specific adaptive immunity is activated by antigen presentation by antigen presenting cells (APCs) and the cytokine microenvironment, and is mainly mediated by the cellular functions of T cells and the production of antibodies by B cells. Unlike most cell types, immune cells regulate their lamin A/C protein expression relatively rapidly to exert their functions, with expression increasing in macrophages, reducing in neutrophils, and increasing transiently in T cells. In this review, we discuss and summarize studies that have addressed the role played by lamin A/C in the functions of innate and adaptive immune cells in the context of human inflammatory and autoimmune diseases, pathogen infections, and cancer.
This study describes the prevalence of vaccine hesitancy associated with the Catalan systematic childhood vaccination calendar and some related psychosocial determinants among paediatric primary care ...nurses in Barcelona (Spain).
Cross-sectional descriptive study. In 2017 we invited the paediatric nurses (N = 165) working in Barcelona public primary health centres with paediatric departments (N = 41) to participate. They answered a questionnaire with sociodemographic and behavioural variables: severity and perceived probability of contracting the diseases of the vaccines in the vaccination schedule; safety and protection offered by each vaccine; and beliefs, social norms, and knowledge about vaccines. Outcome variable was vaccine hesitancy, dichotomized into not hesitant (nurses who would vaccinate their own offspring), and hesitant (including those who would not vaccinate them, those who had doubts and those who would delay the administration of one or more vaccines). We performed bivariate analysis and adjusted logistic regression models.
83% of paediatric nurses (N = 137) agreed to participate. 67.9% had the intention to vaccinate their children of all the vaccines in the systematic schedule. 32.1% of nurses experienced vaccine hesitancy, especially about the HPV (21.9%) and varicella (17.5%) vaccines. The multivariate analysis suggests associations between hesitancy and low perception of the severity of whooping cough (aOR: 3.88; 95%CI:1.32-11.4), low perception of safety of the HPV vaccine (aOR:8.5;95%CI:1.24-57.8), the belief that vaccines are administered too early (aOR:6.09;95%CI:1.98-18.8), and not having children (aOR:4.05;95%CI:1.22-13.3).
Although most paediatric nurses had the intention to vaccinate their own children, almost one-third reported some kind of vaccine hesitancy, mainly related to doubts about HPV and varicella vaccines, as well as some misconceptions. These factors should be addressed to enhance nurses' fundamental role in promoting vaccination to families.
Matrix metalloproteinases are involved in vascular remodeling. Little is known about their immune regulatory role in atherosclerosis. Here we show that mice deficient for MT4-MMP have increased ...adherence of macrophages to inflamed peritonea, and larger lipid deposits and macrophage burden in atherosclerotic plaques. We also demonstrate that MT4-MMP deficiency results in higher numbers of patrolling monocytes crawling and adhered to inflamed endothelia, and the accumulation of Mafb+ apoptosis inhibitor of macrophage (AIM)+ macrophages at incipient atherosclerotic lesions in mice. Functionally, MT4-MMP-null Mafb+AIM+ peritoneal macrophages express higher AIM and scavenger receptor CD36, are more resistant to apoptosis, and bind acLDL avidly, all of which contribute to atherosclerosis. CCR5 inhibition alleviates these effects by hindering the enhanced recruitment of MT4-MMP-null patrolling monocytes to early atherosclerotic lesions, thus blocking Mafb+AIM+ macrophage accumulation and atherosclerosis acceleration. Our results suggest that MT4-MMP targeting may constitute a novel strategy to boost patrolling monocyte activity in early inflammation.
Residents of Nursing Homes (NHs) have suffered greater impacts from the COVID-19 pandemic. However, the rates of COVID-19 in these institutions are heterogeneously distributed. Describing and ...understanding the structural, functional, and socioeconomic differences between NHs is extremely important to avoid new outbreaks.
Analyze inequalities in the cumulative incidences (CIs) and in the mortality rates (MRs) due to COVID-19 in the NHs of Barcelona based on the characteristics of the NHs.
Exploratory ecological study of 232 NHs. The dependent variables were the cumulative incidence and mortality rate due to COVID-19 in NHs between March and June 2020. Structural variables of the NHs were evaluated such as neighborhood socioeconomic position (SEP), isolation and sectorization capacity, occupancy, overcrowding and ownership.
The cumulative incidence and mortality rate were higher in the low SEP neighborhoods and lower in those of high SEP neighborhoods. Regarding the isolation and sectorization capacity, Type B NHs had a higher risk of becoming infected and dying, while Type C had a lower risk of dying than Type A. Greater overcrowding was associated with greater morbidity and mortality, and higher occupancy was associated with higher incidence. The risk of becoming infected and dying in public NHs was significantly higher than for-profit NH.
The social components together with the functional and infrastructure characteristics of the NHs influence the cumulative incidence and the mortality rate by COVID-19. It is necessary to redefine the care model in the NHs to guarantee the health of the residents.
Pathological angiogenesis contributes to cancer progression and chronic inflammatory diseases. In inflammatory bowel disease, the microvasculature expands by intussusceptive angiogenesis (IA), a ...poorly characterized mechanism involving increased blood flow and splitting of pre‐existing capillaries. In this report, mice lacking the protease MT1‐MMP in endothelial cells (MT1iΔEC) presented limited IA in the capillary plexus of the colon mucosa assessed by 3D imaging during 1% DSS‐induced colitis. This resulted in better tissue perfusion, preserved intestinal morphology, and milder disease activity index. Combined in vivo intravital microscopy and lentiviral rescue experiments with in vitro cell culture demonstrated that MT1‐MMP activity in endothelial cells is required for vasodilation and IA, as well as for nitric oxide production via binding of the C‐terminal fragment of MT1‐MMP substrate thrombospondin‐1 (TSP1) to CD47/αvβ3 integrin. Moreover, TSP1 levels were significantly higher in serum from IBD patients and in vivo administration of an anti‐MT1‐MMP inhibitory antibody or a nonamer peptide spanning the αvβ3 integrin binding site in TSP1 reduced IA during mouse colitis. Our results identify MT1‐MMP as a new actor in inflammatory IA and a promising therapeutic target for inflammatory bowel disease.
Synopsis
Inflammatory bowel disease comprising ulcerative colitis and Crohn's disease does not have a universal efficient therapy. This study identifies the molecular axis MT1‐MMP/thrombospondin‐1/αvβ3 integrin/nitric oxide as a target to reduce inflammatory intussusceptive angiogenesis and improve colitis.
Early expansion of the capillaries in the intestinal mucosa during colitis was caused by intussusceptive/splitting angiogenesis (IA).
Deletion of the protease MT1‐MMP from endothelial cells reduced IA and colitis severity.
Thrombospondin‐1 (TSP1) processing by MT1‐MMP promoted nitric oxide production, vasodilation and IA.
High levels of TSP1 were found in sera from patients suffering low active IBD.
Targeting MT1‐MMP/TSP1/αvβ3 integrin/nitric oxide pathway by monoclonal antibodies or minipump‐delivered peptides decreased IA and ameliorates colitis.
Inflammatory bowel disease comprising ulcerative colitis and Crohn's disease does not have a universal efficient therapy. This study identifies the molecular axis MT1‐MMP/thrombospondin‐1/αvβ3 integrin/nitric oxide as a target to reduce inflammatory intussusceptive angiogenesis and improve colitis.
Abstract Background . Splash pads for recreational purposes are widespread. Using these pads can pose a health risk if they lack installation regulation and water quality supervision. Our aim was to ...describe a waterborne disease outbreak caused by Clostridium perfringens and Cryptosporidium spp. in a Barcelona district and the measures taken for its control. Methods . On August 2018, 71 cases of acute gastroenteritis were detected, affecting people who used a splash pad or were in contact with a user. Microbiological and environmental investigations were carried out. A descriptive analysis of the sample and Poisson regression models adjusted for age and sex were performed, obtaining frequencies, median values, and adjusted prevalence ratios with their 95% confidence intervals. Results The median age of the cases was 6.7 years, 27 (38%) required medical care, and three (4.2%) were hospitalized. The greater the number of times a person entered the area, the greater the number of symptoms and their severity. Nineteen (76%) of the 25 stool samples collected from cases showed the presence of one or both pathogens. Environmental investigations showed deficiencies in the facilities and identified the presence of both species in the splash pad. Health education and hygiene measures were carried out, and 14 days after the closure of the facilities, no more cases related to the pad were recorded. Conclusions . Specific regulations are needed on the use of splash pads for recreational purposes. Until these regulations are in place, these types of facility should comply with the regulations that apply to swimming pools and spas, including those related to the design of the tanks, water recirculation systems, and adequate disinfection systems.
Disease surveillance using adequate case definitions is very important. The objective of the study was to compare the performance of influenza case definitions and influenza symptoms in the first two ...epidemic weeks with respect to other epidemic weeks. We analysed cases of acute respiratory infection detected by the network of sentinel primary care physicians of Catalonia for 10 seasons. We calculated the diagnostic odds ratio (DOR) and 95% confidence intervals (CI) for the first two epidemic weeks and for other epidemic weeks. A total of 4,338 samples were collected in the epidemic weeks, of which 2,446 (56.4%) were positive for influenza. The most predictive case definition for laboratory-confirmed influenza was the WHO case definition for influenza-like illness (ILI) in the first two epidemic weeks (DOR 2.10; 95% CI 1.57-2.81) and in other epidemic weeks (DOR 2.31; 95% CI 1.96-2.72). The most predictive symptom was fever. After knowing that epidemic threshold had been reached, the DOR of the ILI WHO case definition in children aged <5 years and cough and fever in this group increased (190%, 170% and 213%, respectively). During influenza epidemics, differences in the performance of the case definition and the discriminative ability of symptoms were found according to whether it was known that the epidemic threshold had been reached or not. This suggests that sentinel physicians are stricter in selecting samples to send to the laboratory from patients who present symptoms more specific to influenza after rather than before an influenza epidemic has been declared.
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