Single Nucleotide Polymorphisms in the Bovine TLR2 Extracellular Domain Contribute to Breed and Species-Specific Innate Immune Functionality
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Abstract
Recent evidence suggests that several cattle breeds may be more resistant to infection with the zoonotic pathogen Mycobacterium bovis . Our data presented here suggests that the response to mycobacterial antigens varies in macrophages generated from Brown Swiss (BS) and Holstein Friesian (HF) cattle, two breeds belonging to the Bos taurus family. Whole genome sequencing of the Brown Swiss genome identified several potential candidate genes, in particular Toll-like Receptor-2 (TLR2), a pattern recognition receptor (PRR) that has previously been described to be involved in mycobacterial recognition. Further investigation revealed single nucleotide polymorphisms (SNP) in TLR2 that were identified between DNA isolated from cells of BS and HF cows. Interestingly, one specific SNP, H326Q, showed a different genotype frequency in two cattle subspecies, Bos (B.) taurus and Bos indicus . Cloning of the TLR2 gene and subsequent gene-reporter and chemokine assays revealed that this SNP, present in BS and Bos indicus breeds, resulted in a significantly higher response to mycobacterial antigens as well as tri-acylated lipopeptide ligands in general. Comparing wild-type and H326Q containing TLR2 responses, wild-type bovine TLR2 response showed clear, diminished mycobacterial antigen responses compared to human TLR2, however bovine TLR2 responses containing H326Q were found to be partially recovered compared to human TLR2. The creation of human:bovine TLR2 chimeras increased the response to mycobacterial antigens compared to the full-length bovine TLR2, but significantly reduced the response compared to the full-length human TLR2. Thus, our data, not only present evidence that TLR2 is a major PRR in the mammalian species-specific response to mycobacterial antigens, but furthermore, that there are clear differences between the response seen in different cattle breeds, which may contribute to their enhanced or reduced susceptibility to mycobacterial infection.
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TLR2 contributes to enhanced innate immune signaling and stronger anti-Mycobacterium bovis responses in Brown Swiss cattle.
“TLR2, a key pattern recognition receptor for mycobacterial antigens, contributes to enhanced innate immune signaling and stronger anti-Mycobacterium bovis responses in Brown Swiss cattle [163].”
From The Genomic Landscape of Cattle: Domestication, Dispersal, and Adaptive Evolution (2026) · cites this paper as [163]
The Results section reports stronger CXCL8 responses in Brown Swiss than Holstein Friesian macrophages to a TLR2 agonist and a mycobacterial protein. But it explicitly reports no significant between-breed difference in response to M. bovis BCG; the Brown Swiss response was significantly greater only than its own untreated control. The study did not test responses to virulent M. bovis. (LLM, conf=0.88)
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References 94 · Cited by 19
Research works printed but not linked: 1
- [88]Godfray C. A Strategy for Chieving Bovine Tuberculosis Free Status for England: 2018 Review. Department for Environment, Food & Rural Affairs, UK Government. (2018).
- Authors
- Bartens, M.-C., Gibson, A. J., Etherington, G. J., Di Palma, F., Holder, A., Werling, D., & Willcocks, S.
- Affiliations
- Royal Veterinary College (GB)
- Earlham Institute (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Corresponding author
- Werling, Dirk
- ORCID
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2021-12-23
- Volume
- 12
- Pages
- 764390-764390
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC8732954
- OpenAlex
- W4226316631
- Cited by
- 19
- References
- 94
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 3
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- TLR2, cattle breeds, Brown Swiss cattle, Holstein cows, cattle, Bos indicus, Mycobacterium bovis, mycobacterial infection susceptibility, innate immunity, macrophages, pattern recognition receptors, species-specific immune response, chemokine response
- MeSH terms
- Animals, Breeding, Cattle, Immunity, Innate, Mycobacterium bovis, Mycobacterium Infections, Mycobacterium tuberculosis, Polymorphism, Single Nucleotide, Toll-Like Receptor 2
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