Assistant Professor
Department of Medicine

Project title: Mechanisms of Macrophage Memory in Immunity to Staphylococcus aureus Infection

Michael R. Yeaman, PhD. – Lundquist Institute, Harbor-UCLA Medical Center / UCLA
Scott G. Filler, M.D. – Lundquist Institute, Harbor-UCLA Medical Center / UCLA
Matteo Pellegrini – UCLA

Multidisciplinary Expertise:
Infectious disease, microbiology, immunology, innate immune memory, epigenetics, macrophage memory, cell biology, molecular immunology

Project Description:
Staphylococcus aureus (SA) is the leading cause of skin and skin structure infections, which serve as a portal of entry for hematogenous invasion.  Treatment for SA infections are complicated by increasing antibiotic resistance.  The goal of this project is to discover mechanisms of protective host immune memory to SA infection.  We found that host macrophages acquire specific innate immune memory against SA that is transferrable to naïve hosts.  This protection is likely mediated by epigenetic modifications.  Similarly, bacterial DNA can also undergo epigenetic modifications that mediate pathogenesis.  Therefore, this research aims to decipher host vs. bacterial epigenetic mechanisms of immune defense vs. pathogenesis during SA infection.  Specifically, we aim to identify macrophage epigenetic signatures that mediate protection, as well as SA epigenetic signatures that facilitate in pathogenesis. Understanding these processes will aid in developing novel anti-infectives and immunotherapies to prevent and treat SA and other multi-drug resistant infections.