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Tick Immune Signaling, Microbiota, and Acquisition of Borrelia burgdorferi and Anaplasma phagocytophilum

Award Number: P01AI138949
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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OVERALL - Abstract The proposed Program Project (P01), entitled “Tick Immune Signaling, Microbiota, and Acquisition of Borrelia burgdorferi and Anaplasma phagocytophilum” aims to understand the molecular mechanisms by which the Ixodes tick immune system recognizes invading microbes, interfaces with resident gut microbiota, and impact pathogen persistence. We discovered two unorthodox tick immune cascades that are (a) involved in microbial recognition by an indirect “cross-kingdom” circuit triggered by a mammalian cytokine acquired in the vector blood meal, or (b) by a direct induction by specific bacterial lipids through an atypical immunodeficiency pathway. We also established that (c) interactions between tick gut microbiota and invading pathogens shape vector physiology and immunity, ultimately impacting the ability of ticks to acquire B. burgdorferi or A. phagocytophilum. Building on these paradigms and by combining the expertise and resources from four institutions with impressive history of research involving tick-borne infections, we will determine how discrete Ixodes tick immune pathways, either independently or synergistically, influence the entry and persistence of two major pathogens, B. burgdorferi and A. phagocytophilum. These microbes constitute the focus of our proposal due to their diverse structural and genetic features, their different lifestyles - either extracellular or intracellular - and the fact that they are responsible for the most prevalent tick-borne infections in the United States and many parts of Europe. This Program Project Grant leverages specific assays, tools and methodologies developed by our laboratories, who have a long history of productive collaboration, and which will be supported by an Administrative Core, and a Tick Resource Core whereby organisms and cell lines will be shared. The proposed aims to achieve the goals of this P01 are 1) Develop a Tick Core that provides the research reagents to all projects and to scientific community; 2) Determine how mammalian factors present in tick blood meal stimulate multiple cross-species immunity signaling pathways impacting persistence of diverse pathogens; 3) Investigate molecular basis of microbial detection in ticks via signaling relays and crosstalk by multiple immune pathways; 4) Examine interactions between tick immunome and gut microbiota and how these events impact persistence of tick-borne pathogens. Altogether, this proposal will increase our fundamental understanding of how tick immune signaling pathways operate and interface with the gut microbiota to influence the ability of diverse tick-borne pathogens to persist in the vector and subsequently infect the vertebrate host. The outreach activities generated by sharing the research data, and resources to the scientific community will plant new seeds of innovative research furthering our knowledge of tick-borne infections. Finally, with the technical and conceptual breakthroughs expected, the P01 will entice a new generation of scientists to be engaged and advance this important, yet neglected field of scientific research.


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: 2025 ( Subtotal = $1,941,828 )
2025	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	6	1/30/2025	COMPETING CONTINUATION	$1,941,828
2025	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	001	5	2/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,941,828

Issue Date FY: 2022 ( Subtotal = $1,537,478 )
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	5	7/28/2022	NON-COMPETING CONTINUATION	$1,537,478
														Subtotal = $1,537,478

Issue Date FY: 2021 ( Subtotal = $1,537,478 )
2021	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	4	6/29/2021	NON-COMPETING CONTINUATION	$1,537,478
														Subtotal = $1,537,478

Issue Date FY: 2020 ( Subtotal = $1,537,478 )
2020	2020	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	3	7/23/2020	NON-COMPETING CONTINUATION	$1,537,478
														Subtotal = $1,537,478

Issue Date FY: 2019 ( Subtotal = $1,537,478 )
2019	2019	UNIVERSITY OF MARYLAND	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	2	7/10/2019	NON-COMPETING CONTINUATION	$1,537,478
														Subtotal = $1,537,478

Issue Date FY: 2018 ( Subtotal = $1,578,353 )
2018	2018	UNIVERSITY OF MARYLAND	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Allergy and Infectious Diseases Research	000	1	7/12/2018	NEW	$1,578,353
														Subtotal = $1,578,353

Grand Total All Awards = $9,670,093

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Tick Immune Signaling, Microbiota, and Acquisition of Borrelia burgdorferi and Anaplasma phagocytophilum

Award Number: P01AI138949

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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