Eomes expression identifies the early bone marrow precursor to classical NK cells.

Natural killer (NK) cells traffic through the blood and mount cytolytic and interferon-γ (IFNγ)-focused responses to intracellular pathogens and tumors. Type 1 innate lymphoid cells (ILC1s) also produce type 1 cytokines but reside in tissues and are not cytotoxic. Whether these differences reflect discrete lineages or distinct states of a common cell type is not understood. Using single-cell RNA sequencing and flow cytometry, we focused on populations of TCF7+ cells that contained precursors for NK cells and ILC1s and identified a subset of bone marrow lineage-negative NK receptor-negative cells that expressed the transcription factor Eomes, termed EomeshiNKneg cells. Transfer of EomeshiNKneg cells into Rag2-/-Il2rg-/- recipients generated functional NK cells capable of preventing metastatic disease. By contrast, transfer of PLZF+ ILC precursors generated a mixture of ILC1s, ILC2s and ILC3s that lacked cytotoxic potential. These findings identified EomeshiNKneg cells as the bone marrow precursor to classical NK cells and demonstrated that the NK and ILC1 lineages diverged early during development.

A Gata3 enhancer necessary for ILC2 development and function.

The type 2 helper effector program is driven by the master transcription factor GATA3 and can be expressed by subsets of both innate lymphoid cells (ILCs) and adaptive CD4+ T helper (Th) cells. While ILC2s and Th2 cells acquire their type 2 differentiation program under very different contexts, the distinct regulatory mechanisms governing this common program are only partially understood. Here we show that the differentiation of ILC2s, and their concomitant high level of GATA3 expression, are controlled by a Gata3 enhancer, Gata3 +674/762, that plays only a minimal role in Th2 cell differentiation. Mice lacking this enhancer exhibited defects in several but not all type 2 inflammatory responses, depending on the respective degree of ILC2 and Th2 cell involvement. Our study provides molecular insights into the different gene regulatory pathways leading to the acquisition of the GATA3-driven type 2 helper effector program in innate and adaptive lymphocytes.

Cost-benefit analysis of preventing nosocomial bloodstream infections among hemodialysis patients in Canada in 2004.

OBJECTIVES: Hemodialysis-associated bloodstream infection (BSI) is a significant public health problem because the number of hemodialysis patients in Canada had doubled from 1996 to 2005.Our study aimed to determine the costs of nosocomial BSIs in Canada and estimate the investment expenses for establishing infection control programs in general hospitals and conduct cost-benefit analysis. MATERIALS AND METHODS: The data from the Canadian Nosocomial Infection Surveillance Program was used to estimate the incidence rate of nosocomial BSI. We used Canadian Institute of Health Information data to estimate the extra costs of BSIs per stay across Canada in 2004. The cost of establishing and maintaining an infection control program in 1985 was estimated by the US Centers for Disease Control and Prevention and converted into 2004 Canadian costs. The possible 20% to 30% reduction of total nosocomial BSIs was hypothesized. RESULTS: A total of 2524 hemodialysis-associated BSIs were projected among 15,278 hemodialysis patients in Canada in 2004. The total annual costs to treat BSIs were estimated to be CDN$49.01 million. Total investment costs in prevention and human resources were CDN$8.15 million. The savings of avoidable medical costs after establishing infection control programs were CDN$14.52 million. The benefit/cost ratio was 1.0 to 1.8:1. CONCLUSION: Our study provides evidence that the economic benefit from implementing infection control programs could be expected to be well in excess of additional cost postinfection if the reduction of BSI can be reduced by 20% to 30%. Infection control offered double benefits: saving money while simultaneously improving the quality of care.