Curli is an amyloid protein produced by Salmonella enterica and other gut microbes as part of their biofilm structure. These biofilms help bacteria adhere to surfaces and evade immune responses. Recent findings suggest that curli may also trigger autoimmunity. A study published in Gut Microbes by Kaitlyn Grando and colleagues provides new insights into how curli interacts with the host immune system.
In individuals with the HLA-B27 gene- a genetic risk factor for reactive arthritis and other inflammatory conditions -the immune system is more susceptible to the stress responses triggered by protein misfolding. The authors showed that curli activates the Unfolded Protein Response (UPR), a stress response that typically restores protein balance, but can lead to chronic inflammation. Using bone marrow-derived macrophages from HLA-B27 transgenic mice, the researchers found curli exposure significantly increased UPR markers.
EbbaBiolight 680 was crucial for visualizing bacterial amyloid interactions with immune cells. Using EbbaBiolight, the authors showed that curli is taken up by gut macrophages, indicating that bacterial amyloids can cross the intestinal barrier and engage with immune cells. EbbaBiolight 680 also revealed curli co-localization with GRP78 - a key chaperone protein involved in UPR activation - suggesting a direct interaction between curli and the UPR pathway. Moreover, it showed how HLA-B27+ hosts show higher numbers of curli-positive cells in infected tissues, correlating with increased inflammation. By providing a clearer picture of how curli contributes to chronic inflammation, this study paves the way for targeting bacterial amyloids in autoimmune and neurodegenerative disease research.
Image: Representative confocal image of cecal tissue from HLA-B27tg mice pre-treated with streptomycin and infected with wild-type Salmonella. The section was stained for nuclei (DAPI, blue), GRP78 (FITC, green) to mark UPR activation, Salmonella (Rhodamine-X, white), and curli (EBBA Biolight 680, red). White arrows indicate macrophages containing both curli and GRP78, confirming the internalization of bacterial amyloids and their interaction with UPR machinery. Image adapted from Figure 7A by Grando, K. et al. (2024) Gut Microbes, 16(1)(CC BY 4.0).