Jordan eliminates leprosy disease and moves to post-elimination surveillance
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GPNMB disrupts SNARE complex assembly to maintain bacterial proliferation within macrophages
Xenophagy plays a crucial role in restraining the growth of intracellular bacteria in macrophages. However, the machinery governing autophagosome‒lysosome fusion during bacterial infection remains incompletely understood. Here, we utilize leprosy, an ideal model for exploring the interactions between host defense mechanisms and bacterial infection. We highlight the glycoprotein nonmetastatic melanoma protein B (GPNMB), which is highly expressed in macrophages from lepromatous leprosy (L-Lep) patients and interferes with xenophagy during bacterial infection. Upon infection, GPNMB interacts with autophagosomal-localized STX17, leading to a reduced N-glycosylation level at N296 of GPNMB. This modification promotes the degradation of SNAP29, thus preventing the assembly of the STX17-SNAP29-VAMP8 SNARE complex. Consequently, the fusion of autophagosomes with lysosomes is disrupted, resulting in inhibited cellular autophagic flux. In addition to Mycobacterium leprae, GPNMB deficiency impairs the proliferation of various intracellular bacteria in human macrophages, suggesting a universal role of GPNMB in intracellular bacterial infection. Furthermore, compared with their counterparts, Gpnmbfl/fl Lyz2-Cre mice presented decreased Mycobacterium marinum amplification. Overall, our study reveals a previously unrecognized role of GPNMB in host antibacterial defense and provides insights into its regulatory mechanism in SNARE complex assembly.
Health inequalities in hepatocellular carcinoma surveillance, diagnosis, treatment, and survival in the United Kingdom: a scoping review
Hepatocellular carcinoma (HCC) remains a deadly cancer in the UK despite advancements in curative therapies. Societal conditions and health inequalities influence the development of chronic liver disease and outcomes from complications including HCC. Scoping this emergent evidence-base is required to inform research and solutions for the NHS.
Pathogens and planetary change
Emerging infectious diseases, biodiversity loss, and anthropogenic environmental change are interconnected crises with massive social and ecological costs. In this Review, we discuss how pathogens and parasites are responding to global change, and the implications for pandemic prevention and biodiversity conservation. Ecological and evolutionary principles help to explain why both pandemics and wildlife die-offs are becoming more common; why land-use change and biodiversity loss are often followed by an increase in zoonotic and vector-borne diseases; and why some species, such as bats, host so many emerging pathogens. To prevent the next pandemic, scientists should focus on monitoring and limiting the spread of a handful of high-risk viruses, especially at key interfaces such as farms and live-animal markets. But to address the much broader set of infectious disease risks associated with the Anthropocene, decision-makers will need to develop comprehensive strategies that include pathogen surveillance across species and ecosystems; conservation-based interventions to reduce human–animal contact and protect wildlife health; health system strengthening; and global improvements in epidemic preparedness and response. Scientists can contribute to these efforts by filling global gaps in disease data, and by expanding the evidence base for disease–driver relationships and ecological interventions.
Air, surface, and wastewater surveillance of SARS-CoV-2; a multimodal evaluation of COVID-19 detection in a built environment
Environmental surveillance of infectious organisms holds tremendous promise to reduce human-to-human transmission in indoor spaces through early detection.
The cellular and molecular cardiac tissue responses in human inflammatory cardiomyopathies after SARS-CoV-2 infection and COVID-19 vaccination
Myocarditis, characterized by inflammatory cell infiltration, can have multiple etiologies, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or, rarely, mRNA-based coronavirus disease 2019 (COVID-19) vaccination. The underlying cellular and molecular mechanisms remain poorly understood. In this study, we performed single-nucleus RNA sequencing on left ventricular endomyocardial biopsies from patients with myocarditis unrelated to COVID-19 (Non-COVID-19), after SARS-CoV-2 infection (Post-COVID-19) and after COVID-19 vaccination (Post-Vaccination). We identified distinct cytokine expression patterns, with interferon-γ playing a key role in Post-COVID-19, and upregulated IL16 and IL18 expression serving as a hallmark of Post-Vaccination myocarditis. Although myeloid responses were similar across all groups, the Post-Vaccination group showed a higher proportion of CD4+ T cells, and the Post-COVID-19 group exhibited an expansion of cytotoxic CD8+ T and natural killer cells. Endothelial cells showed gene expression changes indicative of vascular barrier dysfunction in the Post-COVID-19 group and ongoing angiogenesis across all groups. These findings highlight shared and distinct mechanisms driving myocarditis in patients with and without a history of SARS-CoV-2 infection or vaccination.
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