| First Author | Lacroix-Lamandé S | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 6 | Pages | 2805-14 |
| PubMed ID | 22323544 | Mgi Jnum | J:181854 |
| Mgi Id | MGI:5314282 | Doi | 10.4049/jimmunol.1101987 |
| Citation | Lacroix-Lamande S, et al. (2012) Downregulation of the Na/K-ATPase Pump by Leptospiral Glycolipoprotein Activates the NLRP3 Inflammasome. J Immunol 188(6):2805-14 |
| abstractText | Leptospira interrogans is responsible for a zoonotic disease known to induce severe kidney dysfunction and inflammation. In this work, we demonstrate that L. interrogans induces NLRP3 inflammasome-dependent secretion of IL-1beta through the alteration of potassium transport in bone marrow-derived macrophages. Lysosome destabilization also contributed to the IL-1beta production upon stimulation with live, but not dead, bacteria. Using bone marrow-derived macrophages from various TLRs and nucleotide-binding oligomerization domain-deficient mice, we further determined that IL-1beta production was dependent on TLR2 and TLR4, suggesting a participation of the leptospiral LPS to this process. Hypokaliemia in leptospirosis has been linked to the presence of glycolipoprotein, a cell wall component of L. interrogans that is known to inhibit the expression and functions of the Na/K-ATPase pump. We show in this study that glycolipoprotein activates the inflammasome and synergizes with leptospiral LPS to produce IL-1beta, mimicking the effect of whole bacteria. These results were confirmed in vivo, as wild-type mice expressed more IL-1beta in the kidney than TLR2/4-deficient mice 3 d postinfection with L. interrogans. Collectively, these findings provide the first characterization, to our knowledge, of bacteria-induced activation of the NLRP3 inflammasome through the downregulation of a specific host potassium transporter. |
