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Cutting Edge: Microbial Products Elicit Formation of Dendritic Cell Aggresome-Like Induced Structures in Macrophages¹

Veronica Canadien^*, Tracy Tan, Rachelle Zilber, Jason Szeto^*, Andrew J. Perrin and John H. Brumell^2,*,

^* Infection, Immunity, Injury, and Repair Program, Hospital for Sick Children, and Department of Medical Genetics and Microbiology, and MD/PhD Program, University of Toronto, Toronto, Ontario, Canada

In response to a maturation stimulus, dendritic cells undergo the formation of ubiquitinated protein aggregates known as dendritic cell aggresome-like induced structures (DALIS). DALIS are thought to act as Ag storage structures, allowing for the prioritized degradation of proteins during infection. In this study, we demonstrate that murine macrophages can also form ubiquitinated protein aggregates that are indistinguishable from DALIS. These were formed in a dose- and time-dependent manner, and in response to a variety of microbial products. Surprisingly, the proteasome did not accumulate on these ubiquitinated protein structures, further underlining the difference between DALIS and aggresomes. Our studies suggest that DALIS formation is important for the function of Ag-presenting immune cells during infection.

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