Advances in Immunology and Microbiology Seminar Series: Manish Chauhan

About the event

Featuring research in the areas of:

Epidemiology | Infectious Disease | Disease Ecology | Drug Discovery | Virology |

Global Health | Vector-Borne Disease | Pathology

The Advances in Immunology & Microbiology seminar series is a weekly forum that brings together scientists from diverse fields and disciplines across the College of Veterinary Medicine to discuss research advances in the broad areas of immunology, microbiology, infectious diseases, and global health. Seminars feature student speakers from the Immunology & Infectious Disease (IID) doctoral program, IID-affiliated postdoctoral researchers and faculty, intramural speakers from across the university, and extramural speakers.

PRESENTER: Manish Chauhan, Postdoctoral Research Associate, Goodman Lab, School of Molecular Biosciences

TITLE: STING dependent BAX-IRF3 signaling results in apoptosis during late-stage Coxiella burnetii infection

• Manish Chauhan¹, Chelsea A. Osbron¹, Heather S. Koehler¹, and Alan G. Goodman^1,2*
• ¹School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA
• ²Paul G. Allen School for Global Health, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA
• * Correspondence: alan.goodman@wsu.eduKeywords: Innate immunity, Cyclic di-nucleotides, Reactive oxygen species, Host response, Mouse bone marrow derived macrophages.

ABSTRACT: STING (STimulator of Interferon Genes) cytosolic sensor for cyclic dinucleotides (CDNs), initiate an innate immune response upon binding to CDNs. Coxiella burnetii, an obligate intracellular Gram-negative bacterium, causes the zoonotic disease Q fever. Its ability to inhibit host cell death is pivotal in disease progression. While prior research indicates C. burnetii’s inhibition of host cell apoptosis during early infection stages, late-stage infection sees host cell lysis, releasing bacteria to infect bystander cells. We explored STING’s role during late-stage C. burnetii infection and its impact on host cell death. Loss of STING elevates bacterial loads and suppresses IFNβ and IL6 induction at 12 days post-infection. STING deficiency notably reduces apoptosis via diminished caspase-8 and -3 activation. During infection, STING triggers IRF3 activation, interacting with BAX. BAX translocates to mitochondria, inducing mitochondrial membrane depolarization and increasing cytosolic mtDNA in a STING-dependent manner. Elevated cytosolic mtDNA leads to augmented cytosolic 2’-3’ cGAMP, establishing a positive feedback loop, intensifying STING activation and downstream signaling. In summary, STING signaling is crucial for BAX-IRF3-mediated mitochondria-induced apoptosis during late-stage C. burnetii infection.