| First Author | Vasudevan SO | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 5 | Pages | 110755 |
| PubMed ID | 35508125 | Mgi Jnum | J:344029 |
| Mgi Id | MGI:7283974 | Doi | 10.1016/j.celrep.2022.110755 |
| Citation | Vasudevan SO, et al. (2022) A TLR4-independent critical role for CD14 in intracellular LPS sensing. Cell Rep 39(5):110755 |
| abstractText | Intracellular lipopolysaccharide (LPS) sensing by the noncanonical inflammasome comprising caspase-4 or -11 governs antibacterial host defense. How LPS gains intracellular access in vivo is largely unknown. Here, we show that CD14-an LPS-binding protein with a well-documented role in TLR4 activation-plays a vital role in intracellular LPS sensing in vivo. By generating Cd14(-/-) and Casp11(-/-) mice strains on a Tlr4(-/-) background, we dissociate CD14's known role in TLR4 signaling from its role in caspase-11 activation and show a TLR4-independent role for CD14 in GSDMD activation, pyroptosis, alarmin release, and the lethality driven by cytosolic LPS. Mechanistically, CD14 enables caspase-11 activation by mediating cytosolic localization of LPS in a TLR4-independent manner. Overall, our findings attribute a critical role for CD14 in noncanonical inflammasome sensing of LPS in vivo and establish-together with previous literature-CD14 as an essential proximal component of both TLR4-based extracellular and caspase-11-based intracellular LPS surveillance. |
