244C Poster - 02. Immunity and the microbiome
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Yizhu Mu ^1,3; Anni Kleino ²; Neal silverman ²; Francesca Dicara ^1,3

Affiliations:
1) Dalhousie university, Halifax, NS, Canada; 2) University of Massachusetts Medical School, Worcester, MA, USA; 3) IWK heath center, Halifax, NS, Canada

Keywords:
c. innate immunity; l. lipids in signaling

The Imd pathway plays a pivotal role in the Drosophila defense response against bacterial infection. Gram-negative bacterial infection activates Imd protein which promotes the activation of the NF-κB homolog Relish for the robust antimicrobial peptide gene expression. Although Imd activation is finely regulated, our knowledge of the cellular mechanisms modulating the Imd pathway is still in its infancy. Understanding of the Imd pathway is further complicated by the involvement of Imd protein in the formation and resolution of amyloid-like structures which are indispensable for the activation of the Imd pathway. Peroxisomes are essential lipid metabolic organelles known to play an important role in innate immunity through regulation of cellular lipids milieu in the activated immune cells. Moreover, it is known that defects in peroxisome metabolism inhibits the activation of the Imd pathway. Therefore, we hypothesize that changes in the lipid milieu at the plasma membrane might contribute the Imd amyloid fibril formation and subsequent signaling. Here we demonstrated that peroxisomes regulate Imd amyloid-like structure formation and the activation of the Imd signaling. Using immunofluorescence experiments of Drosophila S2 cells, we found that Gram-negative bacterial infection results in the robust amyloid formation in wild type (WT) S2 cells whereas in the absence of functional peroxisomes (peroxisome depleted cells) amyloid structures are not detected. Furthermore, bacterial infection results in the formation of distinct Imd punctate structures that co-localize with amyloid structure in the WT S2 cells suggesting the activation of the Imd pathway. In contrast, peroxisome deficient S2 cells show impairment in the formation of distinct Imd punctate structures in response to bacterial infection. Furthermore, lipids such as PIP2 and PA (whose biosynthesis are known to require peroxisomes) were found to interact with IMD protein in vitro. Altogether, our initial study shows that peroxisomes play a functional role in the activation of the Imd pathway by regulating IMD amyloid structures formation.