Tuberculosis remains one of the world’s deadliest infectious diseases. About one-third of the wor... more Tuberculosis remains one of the world’s deadliest infectious diseases. About one-third of the world’s population is infected with tuberculosis bacteria. Understanding the dynamics of transmission at different spatial scales is critical to progress in its control. We present an agent-based model for tuberculosis epidemics in Barcelona, which has an observatory on this disease. Our model considers high heterogeneity within the population, including risk factors for developing an active disease, and it tracks the individual behavior once diagnosed. We incorporated the immunodeficiency and smoking/alcoholism, as well as the individual’s origin (foreigner or not) for its contagion and infection as risks factors. We implemented the model in Netlogo, a useful tool for interaction with physicians. However, the platform has some computational limitations, and we propose a solution to overcome them.
Modulation of immunity and disease by glycans is increasingly recognized. However, how host glyco... more Modulation of immunity and disease by glycans is increasingly recognized. However, how host glycosylation shapes and is shaped by tuberculosis remains poorly understood. We show that deficiency in the glucosaminyl (N-acetyl) transferase 1 (Gcnt1), a key enzyme for core-2 O-glycans biosynthesis, drives susceptibility to Mycobacterium tuberculosis infection. The increased susceptibility of Gcnt1 deficient mice was characterized by extensive lung immune pathology, mechanistically related to neutrophils. Uninfected Gcnt1 deficient mice presented bone marrow, blood and lung neutrophilia, which further increased with infection. Blood neutrophilia required Gcnt1 deficiency in the hematopoietic compartment, relating with enhanced granulopoiesis, but normal cellular egress from the bone marrow. Interestingly, for the blood neutrophilia to translate into susceptibility to M. tuberculosis infection, Gnct1 deficiency in the stroma was also necessary. Complete Gcnt1 deficiency associated with in...
Design and objectives A cross-sectional study to evaluate the impact of COVID-19 on the psychosoc... more Design and objectives A cross-sectional study to evaluate the impact of COVID-19 on the psychosocial sphere in both the general population and healthcare workers (HCWs). Methods The study was conducted in Catalonia (Spain) during the first wave of the COVID-19 pandemic when strict lockdown was in force. The study population included all people aged over 16 years who consented to participate in the study and completed the survey, in this case a 74-question questionnaire shared via social media using snowball sampling. A total of 56 656 completed survey questionnaires were obtained between 3 and 19 April 2020. The primary and secondary outcome measures included descriptive statistics for the non-psychological questions and the psychological impact of the pandemic, such as depression, anxiety, stress and post-traumatic stress disorder question scores. Results A n early and markedly negative impact on family finances, fear of working with COVID-19 patients and ethical issues related to ...
Although contacts between tuberculosis patients may result in multiple consecutive infections (MC... more Although contacts between tuberculosis patients may result in multiple consecutive infections (MCI), no experimental animal models consider this fact when used in basic studies. Moreover, the current TB vaccine (BCG) has demonstrated a limited protection in humans. In this study we evaluate the effect of tuberculosis MCI by way of a simple mathematical analysis using data from the low dose aerosol murine experimental model. The results show that a higher number of, or shorter intervals between, multiple consecutive infections reduce the protective effect of BCG. This is due to both the increase in bacillary load at the stationary level of the infection, and the protective immune response induced by the infection itself. This factor must therefore be taken into account when designing new prophylactic strategies as candidate vaccines for the replacement of BCG.
Background: Evaluation of a quick and easy model to determine the intrinsic ability of clinical s... more Background: Evaluation of a quick and easy model to determine the intrinsic ability of clinical strains to generate active TB has been set by assuming that this is linked to the fitness of Mycobacterium tuberculosis strain at the innate phase of the infection. Thus, the higher the bacillary load, the greater the possibility of inducting liquefaction, and thus active TB, once the adaptive response is set. Methodology/Principal Findings: The virulence of seven clinical Mycobacterium tuberculosis strains isolated in Spain was tested by determining the bacillary concentration in the spleen and lung of mice at weeks 0, 1 and 2 after intravenous (IV) inoculation of 104 CFU, and by determining the growth in vitro until the stationary phase had been reached. Cord distribution automated analysis showed two clear patterns related to the high and low fitness in the lung after IV infection. This pattern was not seen in the in vitro fitness tests, which clearly favored the reference strain (H37R...
Tuberculosis (TB) is a leading cause of mortality due to infectious disease, but the factors dete... more Tuberculosis (TB) is a leading cause of mortality due to infectious disease, but the factors determining disease progression are unclear. Transcriptional signatures associated with type I IFN signalling and neutrophilic inflammation were shown to correlate with disease severity in mouse models of TB. Here we show that similar transcriptional signatures correlate with increased bacterial loads and exacerbate pathology during Mycobacterium tuberculosis infection upon GM-CSF blockade. Loss of GM-CSF signalling or genetic susceptibility to TB (C3HeB/FeJ mice) result in type I IFN-induced neutrophil extracellular trap (NET) formation that promotes bacterial growth and promotes disease severity. Consistently, NETs are present in necrotic lung lesions of TB patients responding poorly to antibiotic therapy, supporting the role of NETs in a late stage of TB pathogenesis. Our findings reveal an important cytokine-based innate immune effector network with a central role in determining the outc...
Tuberculosis remains one of the world’s deadliest infectious diseases. About one-third of the wor... more Tuberculosis remains one of the world’s deadliest infectious diseases. About one-third of the world’s population is infected with tuberculosis bacteria. Understanding the dynamics of transmission at different spatial scales is critical to progress in its control. We present an agent-based model for tuberculosis epidemics in Barcelona, which has an observatory on this disease. Our model considers high heterogeneity within the population, including risk factors for developing an active disease, and it tracks the individual behavior once diagnosed. We incorporated the immunodeficiency and smoking/alcoholism, as well as the individual’s origin (foreigner or not) for its contagion and infection as risks factors. We implemented the model in Netlogo, a useful tool for interaction with physicians. However, the platform has some computational limitations, and we propose a solution to overcome them.
Modulation of immunity and disease by glycans is increasingly recognized. However, how host glyco... more Modulation of immunity and disease by glycans is increasingly recognized. However, how host glycosylation shapes and is shaped by tuberculosis remains poorly understood. We show that deficiency in the glucosaminyl (N-acetyl) transferase 1 (Gcnt1), a key enzyme for core-2 O-glycans biosynthesis, drives susceptibility to Mycobacterium tuberculosis infection. The increased susceptibility of Gcnt1 deficient mice was characterized by extensive lung immune pathology, mechanistically related to neutrophils. Uninfected Gcnt1 deficient mice presented bone marrow, blood and lung neutrophilia, which further increased with infection. Blood neutrophilia required Gcnt1 deficiency in the hematopoietic compartment, relating with enhanced granulopoiesis, but normal cellular egress from the bone marrow. Interestingly, for the blood neutrophilia to translate into susceptibility to M. tuberculosis infection, Gnct1 deficiency in the stroma was also necessary. Complete Gcnt1 deficiency associated with in...
Design and objectives A cross-sectional study to evaluate the impact of COVID-19 on the psychosoc... more Design and objectives A cross-sectional study to evaluate the impact of COVID-19 on the psychosocial sphere in both the general population and healthcare workers (HCWs). Methods The study was conducted in Catalonia (Spain) during the first wave of the COVID-19 pandemic when strict lockdown was in force. The study population included all people aged over 16 years who consented to participate in the study and completed the survey, in this case a 74-question questionnaire shared via social media using snowball sampling. A total of 56 656 completed survey questionnaires were obtained between 3 and 19 April 2020. The primary and secondary outcome measures included descriptive statistics for the non-psychological questions and the psychological impact of the pandemic, such as depression, anxiety, stress and post-traumatic stress disorder question scores. Results A n early and markedly negative impact on family finances, fear of working with COVID-19 patients and ethical issues related to ...
Although contacts between tuberculosis patients may result in multiple consecutive infections (MC... more Although contacts between tuberculosis patients may result in multiple consecutive infections (MCI), no experimental animal models consider this fact when used in basic studies. Moreover, the current TB vaccine (BCG) has demonstrated a limited protection in humans. In this study we evaluate the effect of tuberculosis MCI by way of a simple mathematical analysis using data from the low dose aerosol murine experimental model. The results show that a higher number of, or shorter intervals between, multiple consecutive infections reduce the protective effect of BCG. This is due to both the increase in bacillary load at the stationary level of the infection, and the protective immune response induced by the infection itself. This factor must therefore be taken into account when designing new prophylactic strategies as candidate vaccines for the replacement of BCG.
Background: Evaluation of a quick and easy model to determine the intrinsic ability of clinical s... more Background: Evaluation of a quick and easy model to determine the intrinsic ability of clinical strains to generate active TB has been set by assuming that this is linked to the fitness of Mycobacterium tuberculosis strain at the innate phase of the infection. Thus, the higher the bacillary load, the greater the possibility of inducting liquefaction, and thus active TB, once the adaptive response is set. Methodology/Principal Findings: The virulence of seven clinical Mycobacterium tuberculosis strains isolated in Spain was tested by determining the bacillary concentration in the spleen and lung of mice at weeks 0, 1 and 2 after intravenous (IV) inoculation of 104 CFU, and by determining the growth in vitro until the stationary phase had been reached. Cord distribution automated analysis showed two clear patterns related to the high and low fitness in the lung after IV infection. This pattern was not seen in the in vitro fitness tests, which clearly favored the reference strain (H37R...
Tuberculosis (TB) is a leading cause of mortality due to infectious disease, but the factors dete... more Tuberculosis (TB) is a leading cause of mortality due to infectious disease, but the factors determining disease progression are unclear. Transcriptional signatures associated with type I IFN signalling and neutrophilic inflammation were shown to correlate with disease severity in mouse models of TB. Here we show that similar transcriptional signatures correlate with increased bacterial loads and exacerbate pathology during Mycobacterium tuberculosis infection upon GM-CSF blockade. Loss of GM-CSF signalling or genetic susceptibility to TB (C3HeB/FeJ mice) result in type I IFN-induced neutrophil extracellular trap (NET) formation that promotes bacterial growth and promotes disease severity. Consistently, NETs are present in necrotic lung lesions of TB patients responding poorly to antibiotic therapy, supporting the role of NETs in a late stage of TB pathogenesis. Our findings reveal an important cytokine-based innate immune effector network with a central role in determining the outc...
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