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The immune response to mycobacteria is characterized by granuloma formation, which features multinucleated giant cells as a unique macrophage type. We previously found that multinucleated giant cells result from Toll-like receptor-induced DNA damage and cell autonomous cell cycle modifications. However, the giant cell progenitor identity remained unclear. Here, we show that the giant cell-forming potential is a particular trait of monocyte progenitors. Common monocyte progenitors potently produce cytokines in response to mycobacteria and their immune-active molecules. In addition, common monocyte progenitors accumulate cholesterol and lipids, which are prerequisites for giant cell transformation. Inducible monocyte progenitors are so far undescribed circulating common monocyte progenitor descendants with high giant cell-forming potential. Monocyte progenitors are induced in mycobacterial infections and localize to granulomas. Accordingly, they exhibit important immunological functions in mycobacterial infections. Moreover, their signature trait of high cholesterol metabolism may be piggy-backed by mycobacteria to create a permissive niche. Multinucleated giant cells characterize granuloma formation in mycobacterial infections. Here the authors identify monocyte precursors with distinct immunological and metabolic properties as a source of the granuloma multinucleated giant cell compartment.

Immunity in infection, inflammation and malignancy differs markedly in man and mouse. Still, we learn about human immunity in large extent from experimental mouse models. We propose a novel data integration approach which identifies concordant and discordant gene expression patterns of the immune responses in heterologous data sets. We have conducted experiments to compare human and murine transcriptional responses to Mycobacterium tuberculosis (Mtb) infection in whole blood (WB) as well as macrophages and compared them with simulated as well as publicly available data. Our results indicate profound differences between patterns of gene expression in innate and adaptive immunity in man and mouse upon Mtb infection. We characterized differential expression of T-cell related genes corresponding to the differences in phenotype between tuberculosis (TB) highly and low susceptible mouse strains. Our approach is general and facilitates the choice of optimal animal model for studies of the human immune response to a particular disease.

Unexpected pathogen transmission between animals, humans and their shared environments can impact all aspects of society. The Tripartite organisations—the Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the World Organisation for Animal Health (WOAH)—have been collaborating for over two decades. The inclusion of the United Nations Environment Program (UNEP) with the Tripartite, forming the ‘Quadripartite’ in 2021, creates a new and important avenue to engage environment sectors in the development of additional tools and resources for One Health coordination and improved health security globally. Beginning formally in 2010, the Tripartite set out strategic directions for the coordination of global activities to address health risks at the human-animal-environment interface. This paper highlights the historical background of this collaboration in the specific area of health security, using country examples to demonstrate lessons learnt and the evolution and pairing of Tripartite programmes and processes to jointly develop and deliver capacity strengthening tools to countries and strengthen performance for iterative evaluations. Evaluation frameworks, such as the International Health Regulations (IHR) Monitoring and Evaluation Framework, the WOAH Performance of Veterinary Services (PVS) Pathway and the FAO multisectoral evaluation tools for epidemiology and surveillance, support a shared global vision for health security, ultimately serving to inform decision making and provide a systematic approach for improved One Health capacity strengthening in countries. Supported by the IHR-PVS National Bridging Workshops and the development of the Tripartite Zoonoses Guide and related operational tools, the Tripartite and now Quadripartite, are working alongside countries to address critical gaps at the human-animal-environment interface.

BackgroundZoonotic diseases, which are transmissible between animals and humans, account for approximately 75% of emerging human infectious diseases. Management of these diseases is crucial for reducing risks to human and animal populations. The Tripartite Zoonoses Guide (TZG), developed by the Tripartite organisations—Food and Agriculture Organization of the United Nations (FAO), World Health Organization (WHO), and World Organisation for Animal Health (WOAH)—identified workforce capacity as vital in delivering a One Health approach to zoonotic disease prevention, preparedness, and response. Most workforce development efforts are sector-specific. The Workforce development for effective management of zoonotic diseases: Operational tool of the Tripartite Zoonoses Guide (WFD OT) was developed collaboratively by the Tripartite to strengthen cross-sectoral and multidisciplinary workforce capacity.MethodsA landscape analysis was conducted to inform the development of the WFD OT. WHO coordinated a Technical Working Group (TWG) comprising international experts, which convened monthly to guide the development process. The TWG was responsible for designing and developing the core components of the WFD OT, including the workforce functions, occupations, competencies, training programmes, and supporting tools and resources. Following development, the tool was piloted in three countries and officially launched in December 2024.ResultsThe WFD OT provides a detailed framework for managing zoonotic diseases, including 36 functions across five phases of disease management, 57 occupations, 133 competencies, and 383 training programmes. It also provides a database of 196 tools and resources to address various aspects of workforce development. The tool is designed to be flexible, offering delivery options that include in-person, online, or a combination of both formats. The tool can be used independently or with support from FAO, WHO, and WOAH and is intended to be integrated into existing national and sub-national broader workforce strategies.ConclusionsZoonotic diseases present complex One Health challenges that require a competent workforce capable of effective multisectoral collaboration. The WFD OT guides countries to create a comprehensive work plan for strengthening multisectoral workforce capacity.

Over the last several years there has been an increase in studies reporting the presence of microplastic particles (MPs) in both indoor and outdoor air. Data reported reflect a variety of different types of air samples, which have helped to demonstrate the ubiquity of MPs in the atmosphere and their potential contribution to atmospheric particulate matter (PM). The relative quality of the data reporting on MPs in air has not been evaluated, but represents an important step towards improving our overall understanding of the human health implications in relation to inhalation exposure to MPs. Adopting recent approaches that have been proposed to assess the quality of data for those studies reporting concentrations in biota and water samples, we identify a suite of criteria used to screen studies reporting MPs in air for the purposes of evaluating their usefulness in assessing human exposure. Here we review and summarize data from 27 studies reporting MPs in various types of air samples and evaluate each of the studies against 11 separate criteria representing four main categories (sampling; contamination mitigation; sample purification / handling; characterization and application towards assessing human exposure). On average, studies scored 48.6% (range 18.2–81.8%) of the maximum score. Only one study received a positive score for all criteria, implying that there remains a need for future studies to consider strengthening implementation and reporting of QA/QC protocol. The most urgent areas requiring attention relate to the need for studies to avoid and verify background contamination and to strengthen the quantification of method recovery efficiencies. The majority of studies report data for particulates > 10 μm. Due to the associations between exposure to particles < 10 μm and human health effects, we recommend that prioritization efforts that develop standard protocols, based on existing air sampling methods capable of characterizing MPs < 10 μm are progressed.

Myeloid cells encompass distinct populations with unique functions during homeostasis and disease. Recently, a novel subset of innate cells, myeloid-derived suppressor cells (MDSCs), has been described in cancer, which suppresses T-cell responses and fosters disease progression. The role of MDSCs in infection is insufficiently addressed. To examine the presence and function of MDSCs during experimental pulmonary tuberculosis (TB) and further understand the immunologic consequences of direct interactions between MDSCs and lung bacterial pathogens. Using cell-based approaches and experimental mouse models for pulmonary TB we characterized MDSCs as novel myeloid populations directly interacting with Mycobacterium tuberculosis (Mtb). MDSCs readily phagocytosed Mtb, and released proinflammatory (IL-6, IL-1α) and immunomodulatory (IL-10) cytokines while retaining their suppressive capacity. MDSCs were identified at the site of infection in the lung in disease-resistant and -susceptible mice during pulmonary TB. Excessive MDSC accumulation in lungs correlated with elevated surface expression of IL-4Rα and heightened TB lethality, whereas targeted depletion of MDSCs ameliorated disease. Our data reveal that MDSCs provide a niche for pathogen survival and tailor immunity in TB. These findings suggest MDSCs as amenable targets for host-directed therapies and emphasize them as cellular-immune regulators during chronic inflammatory conditions, including chronic infections and microbial complications of neoplastic disorders.

DNA-encoded chemical library (DECL) technology is used by the pharmaceutical industry to discover small molecules capable of modulating biologically relevant targets. DECL synthesis starts with an oligonucleotide that contains a chemical linker moiety, and proceeds through iterative cycles of DNA barcode elongation and chemical synthesis. DECL selections require little protein, minimal assay development and no specialized instrumentation. Parallel DECL selections can be easily conducted, making it possible to directly compare results across different conditions. The acquisition of building blocks is a large impediment when setting up a successful DECL platform. A potential solution is the sharing of building blocks between different labs, or the high-throughput parallel synthesis of novel building blocks. DNA-compatible reactions are required to join the building blocks together, and numerous academic labs have recently taken up this challenge. DECLs exist as unpurified mixtures, complicating data analysis. Machine learning may provide an improved ability to interrogate these data. DECL selections are largely limited to soluble purified proteins. However, progress has been made towards cell surface and in-cell selections. Publication guidelines are needed to better enable reproducibility; for example, the quantification of amplifiable DNA by quantitative PCR, and more complete datasets and building block lists, should be provided.DNA-encoded chemical libraries (DECLs) are used in the discovery of small molecules with potential therapeutic benefit. In this Primer, Satz et al. describe the best practices for DECL synthesis, selection and analysis, as well as requirements to enhance reproducibility between and within groups.

The increased incidence of whooping cough worldwide suggests that current vaccination against Bordetella pertussis infection has limitations in quality and duration of protection. The resurgence of infection has been linked to the introduction of acellular vaccines (aP), which have an improved safety profile compared with the previously used whole-cell (wP) vaccines. To determine immunological differences between aP and wP priming in infancy, we performed a systems approach of the immune response to booster vaccination. Transcriptomic, proteomic, cytometric, and serologic profiling revealed multiple shared immune responses with different kinetics across cohorts, including an increase of blood monocyte frequencies and strong antigen-specific IgG responses. Additionally, we found a prominent subset of aP-primed individuals (30%) with a strong differential signature, including higher levels of expression for CCL3, NFKBIA, and ICAM1. Contrary to the wP individuals, this subset displayed increased PT-specific IgE responses after boost and higher antigen-specific IgG4 and IgG3 antibodies against FHA and FIM2/3 at baseline and after boost. Overall, the results show that, while broad immune response patterns to Tdap boost overlap between aP- and wP-primed individuals, a subset of aP-primed individuals present a divergent response. These findings provide candidate targets to study the causes and correlates of waning immunity after aP vaccination.

In its fiscal year 2015 final rule, the Centers for Medicare & Medicaid Services (CMS) required reporting of tobacco treatment quality measures as part of the Inpatient Psychiatric Facilities Prospective Payment System (IPF PPS). This pre-intervention, post-intervention policy analysis evaluates the impact of that policy at a large academic medical center that opted to improve performance as it implemented reporting measures. Electronic medical record data were collected retrospectively for all adult (≥18 years) inpatient psychiatric admissions from January 1, 2014 to December 31, 2015. Data from admissions were analyzed to determine changes in the provision of tobacco treatment including the proportions of patients screened for tobacco use, receiving tobacco cessation counseling, and receiving tobacco cessation medication(s) using a chi-square test. Covariate analysis of treatment differences based on psychiatric diagnosis was analyzed using Cochran-Mantel-Haenszel and Breslow-Day test. Post-policy screening for admissions increased significantly (85% vs. 97%; p < .001). Referral to cessation counseling increased 18-fold (4% vs. 74%; p < .001). Receipt of Counselling (8% vs. 67%; p < .001) and referral for cessation medication (32% vs. 68%; p < .001) also increased dramatically. Though statistically non-significant, the number of tobacco users who actually received medications increased markedly between 2014 and 2015, 24% versus 35%. Gains in screening, referral, and treatment did not differ by psychiatric diagnosis. The Inpatient Psychiatric Facilities Quality Reporting (IPFQR) Program resulted in a 10-fold increase in the number of smokers who received inpatient tobacco treatment. Should CMS link prospective payment to performance, it could have a major impact on quality of care for tobacco dependence. This is the first study to examine the implementation and impact of new 2015 IPFQR program tobacco measures. This study may illustrate the potential effect that performance based penalties can have should facilities be required to do more than simply report on these tobacco measures. This study exemplifies the impact these new reporting measures can have when psychiatric facilities move beyond letter of the policy, to continually assess organizational performance and implement changes to improve treatment delivery.

Background: Higher smoking prevalence and quantity (cigarettes per day) has been linked to acculturation in the United States among Latinas, but not Latino men. Our study examines variation between a dif­ferent and increasingly important target behavior, smoking level (nondaily vs daily) and acculturation by sex.Methods: An online English-language sur­vey was administered to 786 Latino smokers during July through August 2012. The Brief Acculturation Rating Scale for Mexican Americans–II (ARSMA-II) and other accul­turation markers were used. Multinomial lo­gistic regression models were implemented to assess the association between smoking levels (nondaily, light daily, and moderate/ heavy daily) with acculturation markers.Results: Greater ARMSA-II scores (rela­tive risk ratio, RRR=.81, 95% CI: .72-.91) and being born inside the United States (RRR=.42, 95% CI: .24-.74) were associated with lower relative risk of nondaily smoking. Greater Latino orientation (RRR=1.29, 95% CI: 1.11-1.48) and preference for Spanish language (RRR=1.06, 95% CI: 1.02-1.10) and media (RRR=1.12, 95% CI: 1.05-1.20) were associated with higher relative risk of nondaily smoking. The relationship between acculturation and smoking level did not differ by sex.Conclusion: This study found that among both male and female, English-speaking Latino smokers, nondaily smoking was associated with lower acculturation, while daily smoking was linked with higher ac­culturation.Ethn Dis. 2018.28(2):105-114; doi:10.18865/ed.28.2.105.