Enhanced Preprints

Apoptotic signaling clears engineered Salmonella in an organ-specific manner

  1. Taylor J. Abele
  2. Zachary P. Billman
  3. Lupeng Li
  4. Carissa K. Harvest
  5. Alexia K. Bryan
  6. Gabrielle R Magalski
  7. Joseph P Lopez
  8. Heather N. Larson
  9. Xiao-Ming Yin
  10. Edward A. Miao author has email address
  1. Department of Integrative Immunobiology, Duke University School of Medicine, Durham, NC, USA 27710
  2. Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA 27710
  3. Department of Cell Biology, Duke University School of Medicine, Durham, NC, USA 27710
  4. Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA 27599
  5. Department of Biomedical Engineering, Duke University Pratt School of Engineering, Durham, NC, USA 27710
  6. Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA, USA 70112

Peer review process

Not revised: This Reviewed Preprint includes the authors’ original preprint (without revision), an eLife assessment, and public reviews.

Read more about eLife’s peer review process.

Editors

  • Reviewing Editor
    Russell Vance
    University of California, Berkeley, Berkeley, United States of America
  • Senior Editor
    Mone Zaidi
    Icahn School of Medicine at Mount Sinai, New York, United States of America

Reviewer #1 (Public Review):

In the present manuscript, Abele et al use Salmonella strains modified to robustly induce one of two different types of regulated cell death, pyroptosis or apoptosis in growth phases (when SPI2 T3SS is expressed) and cell types to assess the role of pyroptosis versus apoptosis in systemic versus intestinal epithelial pathogen clearance. They demonstrate that in systemic spread, which requires growth in macrophages, pyroptosis is required to eliminate Salmonella, while in intestinal epithelial cells (IEC), extrusion of the infected cell into the intestinal lumen induced by apoptosis or pyroptosis is sufficient for early pathogen restriction. The methods used in these studies are thorough and well-controlled and lead to robust results, that mostly support the conclusions. The impact on the field is considered minor as the observations are somewhat redundant with previous observations and not generalizable due to cited evidence of different outcomes in other models of infection and a relatively artificial study system that does not permit the assessment of later time points in infection due to rapid clearance. This excludes the study of later effects of differences between pyroptosis and apoptosis in IEC such as i.e. IL-18 and eicosanoid release, which are only observed in the former and can have effects later in infection.

Reviewer #2 (Public Review):

In this study, Abele et al. present evidence to suggest that two different forms of regulated cell death, pyroptosis and apoptosis, are not equivalent in their ability to clear infection with recombinant Salmonella strains engineered to express the pro-pyroptotic NLRC4 agonist, FliC ("FliC-ON"), or the pro-apoptotic protein, BID ("BID-ON"). In general, individual experiments are well-controlled, and most conclusions are justified. However, the cohesion between different types of experiments could be strengthened and the overall impact and significance of the study could be articulated better.

  1. Howard Hughes Medical Institute
  2. Wellcome Trust
  3. Max-Planck-Gesellschaft
  4. Knut and Alice Wallenberg Foundation