is an avian respiratory and reproductive tract pathogen that has a significant economic impact on the poultry industry worldwide. Although membrane proteins of are thought to play crucial roles in host interactions， very few have had their biochemical function defined. In this study， we found that the GroEL protein (Heat shock protein 60) of could induce apoptosis in peripheral blood mononuclear cells and the underlying molecular mechanism was further determined. The GroEL gene from was cloned and expressed in to facilitate the functional analysis of recombinant protein. The purified GroEL protein was shown to adhere to PBMCs and DF-1 cells and cause apoptosis in PBMCs. Protein pulldown assay coupled with mass spectrometry identified that Annexin A2 possibly interacted with GroEL protein. Coimmunoprecipitation assays confirmed that GroEL proteins could bind to Annexin A2 and confocal analysis further demonstrated that GroEL colocolized with Annexin A2 in HEK293T and PBMC cells. Moreover， Annexin A2 expression was significantly induced by a recombinant GroEL protein in PBMCs and knocking down Annexin A2 expression resulted in significantly reduced apoptosis. Taking together， these data suggest that GroEL induces apoptosis in host cells by interacting with Annexin A2， a novel virulence mechanism in Our findings led to a better understanding of molecular pathogenesis in .