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Tick Saliva and Pathogen Transmission

Award Number: R01AI134696
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: 05/09/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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Tick Saliva and Pathogen Transmission - Summary/Abstract: Ticks are ancient hematophagous arthropods that transmit pathogens of public health and veterinary importance. During feeding, they disrupt host homeostasis through salivary molecules that perturb inflammation, blood coagulation and nociception. For more than 100 years, tick saliva has fascinated researchers with its anti-hemostatic, analgesic, and anti-inflammatory properties. Over the previous funding period, we used orthogonal approaches and a cell-centric perspective to better understand the intricate biology occurring between ticks and their hosts. We uncovered that tick extracellular vesicles (EVs) carry bioactive molecules and mediate interspecies communication with mammals. We discovered that tick EVs affect dendritic epidermal T cells (DETCs) and promote distinct outcomes of microbial transmission to mammals. DETCs are a subset of murine γδ T cells located in the skin epidermis that have a critical role in wound healing. DETCs interact with highly specialized epithelial cells (keratinocytes), which comprise approximately 95% of the epidermal layer in the skin. Under homeostasis, epidermal cells differentiate and migrate to the skin surface where they are shed while being replenished at the basal layer or stratum basale. Upon an injury, wound healing occurs in four stages of tissue repair and replacement: hemostasis, inflammation, proliferation, and remodeling. Unfortunately, the epidermis has been mostly neglected when studying the relationship between ticks and their mammalian hosts. For the next iteration of this project (R01 competing renewal), we will investigate the effect of tick EVs on the DETC-keratinocyte dialogue. We will also examine how tick EVs affect the wound healing function of keratinocytes during feeding. Single-cell RNA sequencing, flow cytometry, cell sorting, and murine genetics will be used to uncover how DETCs and keratinocytes communicate during feeding of an ectoparasite. Lineage tracing combined with drug perturbations and allied with sophisticated intravital imaging techniques will be used to track the proliferation, differentiation, and migration of epidermal cells. Our central hypothesis states that tick EVs disrupt the dialogue occurring between DETCs and keratinocytes during feeding altering epidermal wound healing. In Aim #1 of this proposal, we will investigate the effect of tick EVs on the crosstalk between DETCs and keratinocytes. In Aim #2 of this grant application, we will ascertain how tick EVs affect epidermal wound healing during a tick bite and microbial transmission. Collectively, we will provide a distinct biological insight and fill a current gap in knowledge for ectoparasitology and microbial diseases by describing how ticks affect the epidermal environment during feeding.


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: 2026 ( Subtotal = $753,855 )
2026	2026	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	8	6/15/2026	NON-COMPETING CONTINUATION	$753,855
														Subtotal = $753,855

Issue Date FY: 2025 ( Subtotal = $763,576 )
2025	2025	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	001	7	7/7/2025	NON-COMPETING CONTINUATION	$763,576
2025	2022	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	5	2/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $763,576

Issue Date FY: 2024 ( Subtotal = $669,936 )
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	6	7/5/2024	COMPETING CONTINUATION	$669,936
														Subtotal = $669,936

Issue Date FY: 2022 ( Subtotal = $555,415 )
2022	2022	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	001	5	4/26/2022	NON-COMPETING CONTINUATION	$555,415
2022	2021	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	4	3/17/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $555,415

Issue Date FY: 2021 ( Subtotal = $555,415 )
2021	2021	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	4	4/16/2021	NON-COMPETING CONTINUATION	$555,415
														Subtotal = $555,415

Issue Date FY: 2020 ( Subtotal = $555,415 )
2020	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	3	3/13/2020	NON-COMPETING CONTINUATION	$555,415
														Subtotal = $555,415

Issue Date FY: 2019 ( Subtotal = $555,415 )
2019	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	2	3/4/2019	NON-COMPETING CONTINUATION	$555,415
														Subtotal = $555,415

Issue Date FY: 2018 ( Subtotal = $677,669 )
2018	2018	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	1	5/9/2018	NEW	$677,669
														Subtotal = $677,669

Grand Total All Awards = $5,086,696

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Tick Saliva and Pathogen Transmission

Award Number: R01AI134696

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: 05/09/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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