Structure of a central component of the human immune system revealed

An international team of researchers, including three research groups of Ludwig-Maximilians-Universität München (LMU) and Prof. Christian Sieben from the Helmholtz Centre for Infection Research (HZI) in Braunschweig, has now visualized the 3D structure of the ASC speck inside cells using various fluorescence microscopy methods. Recently published in the journal iScience, their study shows that the ASC speck has an amorphous structure with a dense core from which filaments reach out into the periphery. To be able to fully label and image the structure, the researchers had to combine two different approaches. They labeled the less dense periphery of the ASC speck with antibodies and the dense interior with nanobodies.

“When we used just one of the labeling methods, it led to artifacts and thus to data that would be falsely interpreted,” says Prof Christian Sieben, head of the junior research group “Nano Infection Biology” at HZI. "By combining the two approaches, we could overcome this limitation," adds Prof Don Lamb from LMU. This is an important insight for the imaging of dense structures with high-resolution fluorescence microscopy in general. An elegant analysis of the microscopy images of a large number of ASC specks also indicates that as the ASC protein accumulates within the speck, the speck scarcely grows at all, but primarily becomes denser.

“Our results solve the existing controversies in relation to the structure of the ASC speck and are an important step on the road to the complete visualization of the inflammasome in cells,” says Dr Ivo Glück, first author of the new study. “These results could only have been achieved by an international collaboration of leading researchers in the fields of fluorescence microscopy and inflammasome biology. It is a paramount example of modern, interdisciplinary research, which has yielded important insights for several fields,” adds Lamb.