RESUMO
Recent studies suggest that infection reprograms hematopoietic stem and progenitor cells (HSPCs) to enhance innate immune responses upon secondary infectious challenge, a process called "trained immunity." However, the specificity and cell types responsible for this response remain poorly defined. We established a model of trained immunity in mice in response to Mycobacterium avium infection. scRNA-seq analysis revealed that HSPCs activate interferon gamma-response genes heterogeneously upon primary challenge, while rare cell populations expand. Macrophages derived from trained HSPCs demonstrated enhanced bacterial killing and metabolism, and a single dose of recombinant interferon gamma exposure was sufficient to induce similar training. Mice transplanted with influenza-trained HSPCs displayed enhanced immunity against M. avium challenge and vice versa, demonstrating cross protection against antigenically distinct pathogens. Together, these results indicate that heterogeneous responses to infection by HSPCs can lead to long-term production of bone marrow derived macrophages with enhanced function and confer cross-protection against alternative pathogens.
RESUMO
BACKGROUND: Food prescription programs are gaining interest from funders, policy makers, and healthcare payers as a way to provide value-based care. A small body of research suggests that such programs effectively impact health outcomes; however, the quality of existing studies is variable, and most studies use small samples. This study attempts to address these gaps by utilizing a quasi-experimental design with non-equivalent controls, to evaluate clinical outcomes among participants enrolled in a food prescription program implemented at scale. METHODS: We completed a secondary analysis of participant enrollment and utilization data collected between May 2018 and March 2021, by the Houston Food Bank as part of its multi-institution food prescription program. Enrollment data was obtained from 16 health care partners and redemption data from across 40 food pantries in Houston, Texas. Our objective was to assess if program participation impacted multiple cardio-metabolic markers. Exposure was defined as any visit to a food pantry after receipt of prescription. Linear and logistic regression models were used to estimate change in outcomes by exposure status and number of food pantry visits. RESULTS: Exposed patients experienced a -0.28% (p = 0.007) greater change in HbA1c than unexposed patients, over six months. Differences across exposure categories were seen with systolic blood pressure (-3.2, p < 0.001) and diastolic blood pressure (-2.5, p = 0.028), over four months. The odds of any decline in HbA1c (OR = 1.06 per visit, p < 0.001) and clinically meaningful decline in HbA1c (OR = 1.04 per visit, p = 0.007) showed a linear association with visit frequency. CONCLUSIONS: Our study of a large food prescription program involving multiple health care and food pantry sites provides robust evidence of a modest decline in HbA1c levels among participants. These results confirm that food prescription programs can continue to be effective at scale, and portend well for institutionalization of such programs.
