Usage Information
Citation Information: JCI Insight. 2023;8(20):e166242. https://doi.org/10.1172/jci.insight.166242.
Abstract
Host cytosolic sensing of Mycobacterium tuberculosis (M. tuberculosis) RNA by the RIG-I–like receptor (RLR) family perturbs innate immune control within macrophages; however, a distinct role of MDA5, a member of the RLR family, in M. tuberculosis pathogenesis has yet to be fully elucidated. To further define the role of MDA5 in M. tuberculosis pathogenesis, we evaluated M. tuberculosis intracellular growth and innate immune responses in WT and Mda5–/– macrophages. Transfection of M. tuberculosis RNA strongly induced proinflammatory cytokine production in WT macrophages, which was abrogated in Mda5–/– macrophages. M. tuberculosis infection in macrophages induced MDA5 protein expression, accompanied by an increase in MDA5 activation as assessed by multimer formation. IFN-γ–primed Mda5–/– macrophages effectively contained intracellular M. tuberculosis proliferation to a markedly greater degree than WT macrophages. Further comparisons of WT versus Mda5–/– macrophages revealed that during M. tuberculosis infection MDA5 contributed to IL-1β production and inflammasome activation and that loss of MDA5 led to a substantial increase in autophagy. In the mouse TB model, loss of MDA5 conferred host survival benefits with a concomitant reduction in M. tuberculosis bacillary burden. These data reveal that loss of MDA5 is host protective during M. tuberculosis infection in vitro and in vivo, suggesting that M. tuberculosis exploits MDA5 to subvert immune containment.
Authors
C. Korin Bullen, Alok K. Singh, Stefanie Krug, Shichun Lun, Preeti Thakur, Geetha Srikrishna, William R. Bishai
Usage data is cumulative from February 2024 through February 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 741 | 469 |
| 209 | 119 | |
| Figure | 221 | 12 |
| Supplemental data | 68 | 15 |
| Citation downloads | 54 | 0 |
| Totals | 1,293 | 615 |
| Total Views | 1,908 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
