Bioengineering Bacterially Derived Immunomodulants: A Therapeutic Approach to Inflammatory Bowel Disease

Lina Herrera Estrada, Huixia Wu, Kevin Ling, Guikai Zhang, Ronen Sumagin, Charles A. Parkos, Rheinallt M. Jones, Julie A. Champion*, Andrew S. Neish

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Bacterial enteric pathogens have evolved efficient mechanisms to suppress mammalian inflammatory and immunoregulatory pathways. By exploiting the evolutionary relationship between the gut and pathogenic bacteria, we have developed a potential mucosal therapeutic. Our findings suggest that engineered preparations of the Salmonella acetyltransferase, AvrA, suppress acute inflammatory responses such as those observed in inflammatory bowel disease (IBD). We created 125 nm diameter cross-linked protein nanoparticles directly from AvrA and carrier protein to deliver AvrA in the absence of Salmonella. AvrA nanoparticles are internalized in vitro and in vivo into barrier epithelial and lamina propria monocytic cells. AvrA nanoparticles inhibit inflammatory signaling and confer cytoprotection in vitro, and in murine colitis models, we observe decreased clinical and histological indices of inflammation. Thus, we have combined naturally evolved immunomodulatory proteins with modern bioengineering to produce AvrA nanoparticles, a potential treatment for IBD.

Original languageEnglish (US)
Pages (from-to)9650-9662
Number of pages13
JournalACS nano
Volume11
Issue number10
DOIs
StatePublished - Oct 24 2017

Keywords

  • anti-inflammatory
  • colitis
  • effector protein
  • intracellular delivery
  • nanoparticles

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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    Herrera Estrada, L., Wu, H., Ling, K., Zhang, G., Sumagin, R., Parkos, C. A., Jones, R. M., Champion, J. A., & Neish, A. S. (2017). Bioengineering Bacterially Derived Immunomodulants: A Therapeutic Approach to Inflammatory Bowel Disease. ACS nano, 11(10), 9650-9662. https://doi.org/10.1021/acsnano.7b03239