Peer-reviewedCC BY-NC-ND 4.0Proceedings of the National Academy of Sciences of the United States of America
IL36γ signaling promotes mammalian anti-tick immunity
10 affiliations
- 1Department of Veterinary Medicine, University of Maryland, College Park, MD 20740
- 2Center for Cooperative Research in Biosciences (CIC bioGUNE)-Basque Research & Technology Alliance, Derio 48160, Bizkaia, Spain
- 3Neiker- Basque Research & Technology Alliance, Derio 48160, Bizkaia, Spain
- 4Department of Biological Sciences, Texas Tech University, Lubbock, TX 79409
- 5Department of Environmental Health Science, University of Georgia, Athens, GA 30602
- 6Institute of Bioinformatics, University of Georgia, Athens, GA 30602
- 7School of Medicine, Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814
- 8Ikerbasque, Basque Foundation for Science, Bilbao 48011, Bizkaia, Spain
- 9Department of Biological Sciences and Louisiana State University Museum of Natural Science, Louisiana State University, Baton Rouge, LA 70802
- 10Virginia-Maryland College of Veterinary Medicine, College Park, MD 20740
Abstract
Ticks, like Ixodes scapularis, can parasitize a diverse array of vertebrates, favoring natural hosts but feeding opportunistically on others. Natural hosts, as well as permissive hosts such as laboratory mice, tolerate repeated infestations, while many incidental hosts may acquire anti-tick immunity, as first described in guinea pigs. We show that tick-immune guinea pigs display altered dermal cytology and a distinct transcriptome, predominantly upregulating the IL36γ cytokine. Interference with IL36γ signaling, via gene knockdown, chemical inhibition, or its natural antagonist IL36RN, reversed anti-tick immunity in guinea pigs. Conversely, genome engineering to silence IL36RN in C3H mice, representing a permissive host, disrupted tick engorgement, interfering with the transmission of Lyme disease pathogens. These findings firmly establish IL36γ as a central mediator of protective anti-tick immunity involving I. scapularis in mammalian hosts and support future strategies to interfere with tick-transmitted infections.
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BibTeX
@article{kitsou2026il36γ,
title = {{IL36γ signaling promotes mammalian anti-tick immunity}},
author = {Chrysoula Kitsou and Vipin Singh Rana and Min Zhang and Bibek Bhattachan and Preeti Singh and Kamoltip Promnares and Kruthi Vavilikolanu and Shraboni Dutta and Shelby D. Foor and Sandhya Bista and Sarai Araujo-Aris and Xuran Zhuang and Alexis A. Smith and Ana M. Aransay and José Luis Lavín and David Ray and Travis C. Glenn and John Stephen Dumler and Juan Anguita and Brant C. Faircloth and Utpal Pal},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2630481123},
url = {https://doi.org/10.1073/pnas.2630481123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - IL36γ signaling promotes mammalian anti-tick immunity
AU - Chrysoula Kitsou
AU - Vipin Singh Rana
AU - Min Zhang
AU - Bibek Bhattachan
AU - Preeti Singh
AU - Kamoltip Promnares
AU - Kruthi Vavilikolanu
AU - Shraboni Dutta
AU - Shelby D. Foor
AU - Sandhya Bista
AU - Sarai Araujo-Aris
AU - Xuran Zhuang
AU - Alexis A. Smith
AU - Ana M. Aransay
AU - José Luis Lavín
AU - David Ray
AU - Travis C. Glenn
AU - John Stephen Dumler
AU - Juan Anguita
AU - Brant C. Faircloth
AU - Utpal Pal
PY - 2026
DA - 2026/10/21
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2630481123
UR - https://doi.org/10.1073/pnas.2630481123
AB - Ticks, like Ixodes scapularis, can parasitize a diverse array of vertebrates, favoring natural hosts but feeding opportunistically on others. Natural hosts, as well as permissive hosts such as laboratory mice, tolerate repeated infestations, while many incidental hosts may acquire anti-tick immunity, as first described in guinea pigs. We show that tick-immune guinea pigs display altered dermal cytology and a distinct transcriptome, predominantly upregulating the IL36γ cytokine. Interference with IL36γ signaling, via gene knockdown, chemical inhibition, or its natural antagonist IL36RN, reversed anti-tick immunity in guinea pigs. Conversely, genome engineering to silence IL36RN in C3H mice, representing a permissive host, disrupted tick engorgement, interfering with the transmission of Lyme disease pathogens. These findings firmly establish IL36γ as a central mediator of protective anti-tick immunity involving I. scapularis in mammalian hosts and support future strategies to interfere with tick-transmitted infections.
SN - 0027-8424
SN - 1091-6490
ER -