RESUMO
Host defenses against pathogens are energetically expensive, leading ecological immunologists to postulate that they might participate in energetic trade-offs with other maintenance programs. However, the metabolic costs of immunity and the nature of physiologic trade-offs it engages are largely unknown. We report here that activation of immunity causes an energetic trade-off with the homeothermy (the stable maintenance of core temperature), resulting in hypometabolism and hypothermia. This immunity-induced physiologic trade-off was independent of sickness behaviors but required hematopoietic sensing of lipopolysaccharide (LPS) via the toll-like receptor 4 (TLR4). Metabolomics and genome-wide expression profiling revealed that distinct metabolic programs supported entry and recovery from the energy-conserving hypometabolic state. During bacterial infections, hypometabolic states, which could be elicited by competition for energy between maintenance programs or energy restriction, promoted disease tolerance. Together, our findings suggest that energy-conserving hypometabolic states, such as dormancy, might have evolved as a mechanism of tissue tolerance.
Assuntos
Regulação da Temperatura Corporal/imunologia , Imunidade Inata/fisiologia , Imunidade/fisiologia , Animais , Regulação da Temperatura Corporal/fisiologia , Metabolismo Energético/imunologia , Metabolismo Energético/fisiologia , Feminino , Tolerância Imunológica/imunologia , Tolerância Imunológica/fisiologia , Masculino , Metabolismo/imunologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Individuals with serious mental illness often do not receive guideline-concordant metabolic screening and human immunodeficiency virus (HIV) testing, contributing to increased morbidity and premature mortality. This study evaluates the effectiveness of CRANIUM (Cardiometabolic Risk Assessment and treatment through a Novel Integration model for Underserved populations with Mental illness), an intervention to increase metabolic screening and HIV testing among patients with serious mental illness in a community mental health clinic compared to usual care. METHODS: The study used a quasi-experimental design, prospectively comparing a preventive care screening intervention at one community mental health clinic (n = 536 patients) to usual care at the remaining clinics within an urban behavioural health system (n = 4,847 patients). Psychiatrists at the intervention site received training in preventive health screening and had access to a primary care consultant, screening and treatment algorithms, patient registries, and a peer support specialist. Outcomes were the change in screening rates of A1c, lipid, and HIV testing post-intervention at the intervention site compared to usual care sites. RESULTS: Rates of lipid screening and HIV testing increased significantly at the intervention site compared to usual care, with and without multivariable adjustment [Lipid: aOR 1.90, 95% CI 1.32-2.75, P = .001; HIV: aOR 23.42, 95% CI 5.94-92.41, P < .001]. While we observed a significant increase in A1c screening rates at the intervention site, this increase did not persist after multivariable adjustment (aOR 1.37, 95% CI .95-1.99, P = .09). CONCLUSIONS: This low-cost, reverse integrated care model targeting community psychiatrist practices had modest effects on increasing preventive care screenings, with the biggest effect seen for HIV testing rates. Additional incentives and structural supports may be needed to further promote screening practices for individuals with serious mental illness.
Assuntos
Infecções por HIV , Saúde Mental , Humanos , Hemoglobinas Glicadas , Infecções por HIV/diagnóstico , Teste de HIV , Crânio , LipídeosRESUMO
Research on climate change and mental health is a new but rapidly growing field. To summarise key advances and gaps in the current state of climate change and mental health studies, we conducted a scoping review that comprehensively examined research methodologies using large-scale datasets. We identified 56 eligible articles published in Embase, PubMed, PsycInfo, and Web of Science between Jan 1, 2000, and Aug 9, 2020. The primary data collection method used was surveys, which focused on self-reported mental health effects due to acute and subacute climate events. Other approaches used administrative health records to study the effect of environmental temperature on hospital admissions for mental health conditions, and national vital statistics to assess the relationship between environmental temperature and suicide rates with regression analyses. Our work highlights the need to link population-based mental health outcome databases to weather data for causal inference. Collaborations between mental health providers and data scientists can guide the formation of clinically relevant research questions on climate change.
Assuntos
Mudança Climática , Suicídio , Humanos , Saúde Mental , Projetos de Pesquisa , TemperaturaRESUMO
Microbial dysbiosis and inflammation are implicated in diet-induced obesity and insulin resistance. However, it is not known whether crosstalk between immunity and microbiota also regulates metabolic homeostasis in healthy animals. Here, we report that genetic deletion of tuberous sclerosis 1 (Tsc1) in CD11c+ myeloid cells (Tsc1f/fCD11cCre mice) reduced food intake and body mass in the absence of metabolic disease. Co-housing and fecal transplant experiments revealed a dominant role for the healthy gut microbiota in regulation of body weight. 16S rRNA sequencing, selective culture, and reconstitution experiments further confirmed that selective deficiency of Lactobacillus johnsonii Q1-7 contributed to decreased food intake and body mass in Tsc1f/fCD11cCre mice. Mechanistically, activation of mTORC1 signaling in CD11c cells regulated production of L. johnsonii Q1-7-specific IgA, allowing for its stable colonization in the gut. Together, our findings reveal an unexpected transkingdom immune-microbiota feedback loop for homeostatic regulation of food intake and body mass in mammals.