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Host Response and Immunity to Yersenia pestis Infection

Award Number: R01AI129996
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/08/2017
PERIOD OF PERFORMANCE END DATE: 04/30/2023

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Host Response and Immunity to Yersenia pestis Infection - PI: Anderson, Deborah M Project Summary “Host response and immunity to Yersinia pestis infection” Project Summary Type I interferons are expressed by eukaryotic cells upon intracellular invasion by microbial pathogens and they induce a potent anti-viral response. Yet during bacterial infection, expression of type I IFN often leads to a pathologic response that depletes populations of immune effector cells necessary to mediate clearance. Our laboratory has shown that type I IFN signaling contributes to neutrophil depletion during infection by Yersinia pestis, a Gram-negative bacterium that is the causative agent of the plague. Bubonic plague is a highly infectious vector borne disease that can be transmitted through the respiratory route and disseminated through the vasculature of its victims. Septicemic and pneumonic plagues involve the rapid development of an uncontrolled systemic inflammatory response that causes the clinical collapse of the patient, even with antibiotic treatment. These three forms of plague have been responsible for three major pandemics and still cause annual cases of human disease with a high mortality rate worldwide including a hotspot in the Southwestern United States. To date, little about the host responses that directly or indirectly contribute to the progression of plague. Such responses may present new strategies to approach the post- symptomatic treatment of plague and other acute inflammatory diseases. In this application, we propose to study interactions between phagocytic cells and Y. pestis that are responsible for inducing inflammatory responses that contribute to the progression of infection in a murine model. We have identified the broadly conserved Toll-like receptor 7 (TLR7) as activated during infection by wild type Y. pestis. Activation of TLR7 by Y. pestis triggers a non-canonical signaling pathway that induces the expression of type I IFN and its downstream IFN stimulated genes which subsequently interfere with the neutrophilic response and promote the progression of disease. In this project, we aim to understand the molecular signaling events of this novel pathway and their role during infection with Y. pestis. Our long term goal is to use the information gained from this program to better understand innate immune response to bacterial infection and develop host-targeted therapeutics that broadly protect from acutely inflammatory infectious diseases such as the infamous pneumonic plague.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Allergy and Infectious Diseases Research	000	5	2/16/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $365,222 )
2021	2021	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Allergy and Infectious Diseases Research	000	5	4/8/2021	NON-COMPETING CONTINUATION	$365,222
														Subtotal = $365,222

Issue Date FY: 2020 ( Subtotal = $365,705 )
2020	2020	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Allergy and Infectious Diseases Research	000	4	4/9/2020	NON-COMPETING CONTINUATION	$365,705
														Subtotal = $365,705

Issue Date FY: 2019 ( Subtotal = $366,176 )
2019	2019	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Allergy and Infectious Diseases Research	000	3	3/26/2019	NON-COMPETING CONTINUATION	$366,176
														Subtotal = $366,176

Issue Date FY: 2018 ( Subtotal = $366,637 )
2018	2018	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Allergy and Infectious Diseases Research	000	2	4/13/2018	NON-COMPETING CONTINUATION	$366,637
														Subtotal = $366,637

Issue Date FY: 2017 ( Subtotal = $373,364 )
2017	2017	UNIVERSITY OF MISSOURI SYSTEM	316 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Allergy and Infectious Diseases Research	000	1	5/8/2017	NEW	$373,364
														Subtotal = $373,364

Grand Total All Awards = $1,837,104

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Host Response and Immunity to Yersenia pestis Infection

Award Number: R01AI129996

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/08/2017

PERIOD OF PERFORMANCE END DATE: 04/30/2023

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