Activation and evasion of innate immune signaling pathways by Yersinia pestis
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Yersinia pestis is a bacterial pathogen that causes the disease plague in mammals. The disease is rapidly lethal and infected individuals can succumb to the disease in as less as three days post-infection. This suggests that the immune system completely fails at restricting bacterial growth and eliminating the bacteria from the body. We therefore used Y. pestis to study its interactions with the mammalian immune system to gain a deeper understanding of the pathogens strategy to overcome immune responses. We identified that Y. pestis activates Toll-like receptor 7 (TLR7), traditionally considered a mammalian sensor of virus infections. We further demonstrate that this bacterium activates TLR7 to promote mammalian immune cells to produce the type I interferon (IFN), interferon beta, a cytokine released by cells of the immune system in response to infection. In this work we demonstrate that TLR7 and type I IFN are vital for Y. pestis to cause plague. Moreover, we show that this bacterium triggers a previously unknown immune signaling pathway in mammalian immune cells. Since we showed that TLR7 and type I IFN are required for this pathogen to cause plague we can potentially use this information to better design therapeutic strategies that potentiate immune responses. Such strategies can help us move away from the extensive use of antibiotics and circumvent the emerging problem of antibiotic resistance.
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