Sci Adv
Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
Published: January 2025
(MTB) ESX-1, a type VII secretion system, is a key virulence determinant contributing to MTB's survival within lung mononuclear phagocytes (MNPs), but its effect on MNP recruitment and differentiation remains unknown. Here, using multiple single-cell RNA sequencing techniques, we studied the role of ESX-1 in MNP heterogeneity and response in mice and murine bone marrow-derived macrophages (BMDM). We found that ESX-1 is required for MTB to recruit diverse MNP subsets with high MTB burden. Further, MTB induces a transcriptional signature of immune evasion in lung macrophages and BMDM in an ESX-1-dependent manner. Spatial transcriptomics revealed an up-regulation of permissive features within MTB lesions, where monocyte-derived macrophages concentrate near MTB-infected cells. Together, our findings suggest that MTB ESX-1 facilitates the recruitment and differentiation of MNPs, which MTB can infect and manipulate for survival. Our dataset across various models and methods could contribute to the broader understanding of recruited cell heterogeneity during MTB lung infection.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734715 | PMC |
http://dx.doi.org/10.1126/sciadv.adq8158 | DOI Listing |
Bioorg Med Chem Lett
January 2025
Calibr-Skaggs Institute for Innovative Medicines, a division of Scripps Research, La Jolla, CA 92037, United States. Electronic address:
Screening of the ChemDiv molecular library in cholesterol media against Mycobacterium tuberculosis (Mtb) H37Rv strain identified a novel isoxazole thiophene hit as a putative Rv1625c/Cya activator with a promising in vitro activity and good pharmacokinetic properties. Twenty-nine analogs were synthesized to assess the structure-activity relationships (SAR) to further improve potency. The most notable analog was P15, which showed an intramacrophage EC = 1.
View Article and Find Full Text PDFJ Clin Med
January 2025
Oral Health Sciences Department of Periodontology and Oral Implantology, Ghent University, 9000 Ghent, Belgium.
As gingivitis prevalence is closely related to plaque accumulation, effective oral hygiene is mandatory for maintaining healthy gingival tissues. The aim of this study was to evaluate the impact of different toothbrushing methods (a manual toothbrush (group 1 = MTB, the control); an electric toothbrush (group 2 = ETB); and an electric toothbrush with daily visual feedback (group 3 = ETBV)) on the plaque levels and periodontal health in patients after receiving initial periodontal treatment. : A total of 67 patients were initially screened in this study, and 60 patients were randomly allocated into 1 of the 3 groups, with 53 patients completing this study.
View Article and Find Full Text PDFJ Clin Med
January 2025
Tecnun, School of Engineering, University of Navarra, 20018 San Sebastian, Spain.
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View Article and Find Full Text PDFMicroorganisms
January 2025
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
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View Article and Find Full Text PDFMicroorganisms
January 2025
Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
Tuberculosis (TB) remains the major cause of mortality and morbidity, causing approximately 1.3 million deaths annually. As a highly successful pathogen, () has evolved numerous strategies to evade host immune responses, making it essential to understand the interactions between and host cells.
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