The Effect of Bacterial High Temperature Protein G on Intestinal Epithelial Cells in the Context of Pediatric Crohn’s Disease

Abstract

Crohn’s disease (CD), a type of inflammatory bowel disease, is caused by environmental, microbial, genetic, and immunological factors. Increased expression of specific heat shock proteins (HSPs) in CD patients protects intestinal epithelial cells (IECs) from death. High temperature protein G (HtpG), a gene encoding a bacterial HSP, is less abundant in pediatric CD patients than in healthy individuals. The role of HtpG in CD is poorly understood, thus I sought to describe HtpG activity on the innate immune response of IECs. I used metagenomic sequencing data to determine that only certain HtpG lineages appear in the intestines. By measuring IEC inflammatory mediators, I observed HtpG to be inflammatory, but with the capacity to dampen the effects of another inflammatory molecule, tumor necrosis factor. I also identified, by co-affinity purification, that HtpG interacts with three common CD-associated gene variants. These results suggest HtpG acts extra- and intra-cellularly to mediate inflammatory signaling.