Download 2016 department of medicine research day

2016 DEPARTMENT OF MEDICINE RESEARCH DAY
Title of Poster: Staphylococcus aureus coopts cGAS-STING dependent type I
interferon to subvert cutaneous host defense
Presenter: Philip Scumpia
Division: Dermatology
☒ Faculty ☐ Fellow ☐ Resident ☐ Post-doc Research Fellow ☐ Graduate Student ☐ Medical Student ☐Other
Principal Investigator/Mentor: Stephen Smale
Thematic Poster Category:
Atherosclerosis
Co-Investigators:
Infections, Injury and Repair, Inflammation, Host Defense, Immunology, Hemostasis and
Abstract
Staphylococcus aureus is a commensal microorganism that resides on skin, but can cause severe skin
and soft tissue infections once it invades epithelial surfaces. Understanding the initial interactions of S.
aureus with innate immune cells may help identify immune pathways critical to host defense. To this
end, we compared the early transcriptomic response of macrophages treated with live S. aureus (LSA)
with those treated with heat-killed S. aureus (HKSA) to determine early immune pathways activated
by infection. Using this approach, we identify the four major transcriptional programs activated early
in macrophages by LSA. Two transcriptional programs induced by live bacteria: a type I interferon
(IFN) antiviral response and a program important for initiating T cell differentiation required stimulator
of interferon genes (STING) signaling for maximal induction. Activation of the STING programs
requires live bacteria, and largely depends on activation of the DNA sensor cyclic guanosine-adenosine
synthase (cGAS). Non-virulent S. epidermidis and virulent S. aureus strains also induce IFN- through
STING, suggesting it as a common pathway triggered by Staphylococcal species. Cutaneous infection
of STINGgt/gt mice with S. aureus results in impaired IFN- but higher levels of protective interleukin
(IL)-1 and IL-12, enhanced neutrophil recruitment and activity, and improved clearance of S. aureus.
Taken together, we identify early STING activation by S. aureus as a novel immune pathway exploited
by S. aureus to suppress neutrophil dependent host defense.