Giandor Saltz Gigley Molecuar Biology Lab INBRE Spring 2016

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Presentation transcript:

Giandor Saltz Gigley Molecuar Biology Lab INBRE Spring 2016 Define NK Cell Impact on Early CD8 T cell Responses to Toxoplasma gondii Infection Giandor Saltz Gigley Molecuar Biology Lab INBRE Spring 2016

Outline The Immune System and NK Cells Role of NK cells in viral infections Chronic Infections and Immune Exhaustion T. gondii Research Question Experimental Procedure Results Conclusion Questions

The Immune System

Natural Killer Cells Functions: Detection of stressed or non-self cells Cytotoxic Cytokine production University of Minnesota, 2016

Chronic Infection Chronic Infection – Immune system controls infection, but cannot clear it completely 90% of population has a chronic infection Susceptible to chronic infection reactivation: Immunosuppressed groups: HIV/AIDS, Cancer patients, Organ transplant patients, Autoimmune disease

Why do we get Chronic Infections? Immune Exhaustion – Immune System still functional, but tired CD8 T cells important for long term control, affected by immune exhaustion Reasons for developing immune exhaustion are unknown

Role of NK cells in Immune Exhaustion NK cells important in control of acute infections Role of NK cells in infection is more complex than originally thought – implicated in immune exhaustion Viral Infections Early depletion of NK cells in persistent viral infections is therapeutic (Waggoner et al, 2014)

Toxoplasma gondii Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. All rights reserved Photo: D. Ferguson, Oxford University)

Research Question What happens to the CD8 T cell response to T. gondii when you eliminate NK cells early in infection?

Experimental Procedure 3 groups of mice: Naïve, Parasite Infected, Parasite Infected/NK depleted 4 males in each group 6 weeks of age Infected with 10 cysts Depleted NK cells Days -1, 0, 3, and 5 (Antibody PK136) Harvested spleens Day 7 Analyze CD8 T cell response (IFNγ production) by Flow Cytometry

Results Naive D7 ME49 NK- D7 ME49 CD8 IFN-gamma Frequency Absolute Number Absolute # IFNg+ CD8 T cells X 10^5 % CD8 T cells IFNg+

Conclusions What happens to the CD8 T cell response to T. gondii when you eliminate NK cells early in infection? Viral model: Eliminating NK cells early in infection improves CD8 T cell response T. gondii: Eliminating NK cells early in infection decreases CD8 T cell response

Thank you! Funding: INBRE Spring 2016 Dr. Jason Gigley and Lab Members: Daria Ivanova Steve Denton David Stevenson David Rach Kevin Fettel Dominic Cancino Rida Fatima

Audience Questions