Is Receptor-Interacting Protein Kinase 3 a viable therapeutic target for Mycobacterium tuberculosis infection?
- Author(s)
- Stutz, MD; Ojaimi, S; Ebert, G; Pellegrini, M;
- Journal Title
- Frontiers in Immunology
- Publication Type
- Journal Article
- Abstract
- 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-1beta, 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.
- Publisher
- Frontiers Media
- Research Division(s)
- Infection And Immunity
- PubMed ID
- 29892302
- Publisher's Version
- https://doi.org/10.3389/fimmu.2018.01178
- Open Access at Publisher's Site
https://doi.org/10.3389/fimmu.2018.01178- NHMRC Grants
- NHMRC/1006592, NHMRC/1045549, NHMRC/106562, NHMRC/1056282,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-06-26 12:34:43
Last Modified: 2018-06-26 01:22:11