The dwindling list of antimicrobial agents exhibiting broad efficacy against clinical strains of Mycobacterium tuberculosis (Mtb) has forced the medical community to redefine current approaches to the treatment of tuberculosis (TB). Host receptor-interacting protein kinase 3 (RIPK3) has been flagged recently as a potential target, given that it is believed to regulate necroptosis-independent signaling pathways, which have been implicated in exacerbating several inflammatory conditions and which reportedly play a role in the necrosis of Mtb-infected macrophages. To examine the therapeutic potential of inhibiting RIPK3, we infected RIPK3-deficient mice with aerosolized Mtb. We found that the loss of RIPK3 did not alter overall disease outcomes, with deficient animals harboring similar bacterial numbers in the lungs and spleens compared to their wild-type counterparts. Mtb-infected macrophages were not rescued from dying by Ripk3 deletion, nor did this affect production of the pro-inflammatory cytokine IL-1β, both in vitro and in vivo. Infiltration of immune cells into the lungs, as well as the activation of adaptive immunity, similarly was not overtly affected by the loss of RIPK3 signaling. Collectively, our data argue against a role of RIPK3 in mediating pathological inflammation or macrophage necrosis during Mtb disease pathogenesis and thus suggest that this host protein is unlikely to be an attractive therapeutic target for TB.
Pubmed ID: 29892302 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Commercial instrument and chemical vendor. Developer and manufacturer of specialized technological products for life science research and clinical diagnostics markets.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis monoclonal targets IFN-γ
View all literature mentionsThis monoclonal targets CD69
View all literature mentionsThis monoclonal targets CD279 (PD-1)
View all literature mentionsThis monoclonal targets Ly-6G and Ly-6C
View all literature mentionsThis monoclonal targets CD11c
View all literature mentionsThis monoclonal targets CD19
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD16 / CD32
View all literature mentionsThis monoclonal targets TNF-alpha
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsImaging software used to acquire and analyze images from specific Bio-Rad imaging systems. Users can analyze gel or blot features, capture optimized image data, and generate a report of the data. Image Lab software exclusively runs on the Gel Doc EZ imager, Gel Doc XR+ imaging system, ChemiDo MP, ChemiDoc XRS+ imaging systems, Criterion Stain Free imager, and the GS-900calibrated densitometer.
View all literature mentionsThis monoclonal targets IFN-γ
View all literature mentionsThis monoclonal targets CD69
View all literature mentionsThis monoclonal targets CD279 (PD-1)
View all literature mentionsThis monoclonal targets Ly-6G and Ly-6C
View all literature mentionsThis monoclonal targets CD11c
View all literature mentionsThis monoclonal targets CD19
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD16 / CD32
View all literature mentionsThis monoclonal targets TNF-alpha
View all literature mentionsImaging software used to acquire and analyze images from specific Bio-Rad imaging systems. Users can analyze gel or blot features, capture optimized image data, and generate a report of the data. Image Lab software exclusively runs on the Gel Doc EZ imager, Gel Doc XR+ imaging system, ChemiDo MP, ChemiDoc XRS+ imaging systems, Criterion Stain Free imager, and the GS-900calibrated densitometer.
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentions