Hierarchical Cell Death Program Disrupts the Intracellular Niche Required for Burkholderia thailandensis Pathogenesis
David E. Place, Shelbi Christgen, Shraddha Tuladhar, Peter Vogel, R. K. Subbarao Malireddi, Thirumala‐Devi Kanneganti
Abstract
Burkholderia infections result in a high degree of mortality when left untreated; therefore, understanding the host immune response required to control infection is critical. In this study, we uncovered a hierarchical cell death program utilized by infected cells to disrupt the intracellular niche of Burkholderia thailandensis by limiting bacterial intercellular spread, host cell-cell fusion, and bacterial replication. In macrophages, combined loss of key PANoptosis components results in extensive B. thailandensis infection-induced cell-cell fusion, bacterial replication, and increased cell death at later stages of infection compared with both wild-type (WT) and pyroptosis-deficient cells.