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bioRxiv · 10.64898/2026.08.05.743136

Evolution of the proinflammatory receptor TREM-1 in mammals reveals signatures of pathogen-driven conflict

Aleru, O.·Bunn, K. E.·Barber, M. F.
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Abstract

Animal immune cells express a range of surface receptors that promote the detection of diverse host and pathogen-derived molecules. The triggering receptors expressed on myeloid cells (TREMs) encompass a family of cell surface receptors involved in the modulation of immune signaling cascades. Mammalian TREM-1 has emerged as a critical mediator of antibacterial immune defense and inflammatory disease, yet much remains unknown regarding its evolution and relevant molecular interactions. Here we applied a comparative phylogenetic approach to investigate patterns of divergence and natural selection among mammalian TREM-1 orthologs. We identify evidence of repeated positive selection acting within the extracellular ligand binding domain of TREM-1 among primates, rodents, and particularly bats. Structural simulations further suggest that genetic variation in TREM-1 impacts recognition of putative host and microbial ligands, with implications for downstream signaling functions. Together our findings identify patterns of rapid divergence in mammalian TREM-1, suggesting a history of evolutionary conflict in response to pathogen antagonism.

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Aleru, O., Bunn, K. E., Barber, M. F.. 2026-08-09. Evolution of the proinflammatory receptor TREM-1 in mammals reveals signatures of pathogen-driven conflict. https://doi.org/10.64898/2026.08.05.743136

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