Abstract Bats are considered natural hosts for numerous viruses. Their ability to carry viruses that cause severe diseases or even death in other mammals without falling ill themselves has attracted widespread research attention. Toll-like receptor 2 (TLR2) forms heterodimers with TLR1 or TLR6 on cell membranes, recognizing specific pathogen-associated molecular patterns and playing a key role in innate immune responses. Previous studies have shown that moderate TLR2-mediated immune signals aid in pathogen clearance, while excessive or inappropriate TLR2-mediated immune signals can cause self-damage. In this study, we observed that TLR2, unlike TLR1 or TLR6, has undergone relaxed selection in bats compared to other mammals, indicating a reduced functional constraint on TLR2 specifically in bats. Indeed, our cell-based functional assays demonstrated that the ability of TLR2 to bind with TLR1 or TLR6 was significantly reduced in bats, leading to dampened inflammatory signaling. We identified mutations unique to bats that were responsible for this observation. Additionally, we found that mutations at residues 375 and 376 of TLR2 in the common ancestor of bats also resulted in reduced inflammatory response, suggesting that this reduction occurred early in bat evolution. Together, our study reveals that the TLR2-mediated inflammatory response has been specifically dampened in bats, which may be one of the reasons why they could harbor many viruses without falling ill.

Jiaming Zeng

Xiangyi Zhang

Chen Huang

Shilin Tian

Huabin Zhao

Molecular Biology and Evolution

MOLECULAR BIOLOGY AND EVOLUTION 在分子（包括基因组学）和进化生物学的界面发表研究。我们考虑包含人口、分类、功能和表型组织各个层次的模式、过程和预测的手稿。除了具有更广泛范围和影响的基本发现外，我们还对出版新的和改进的方法、资源、技术和理论感兴趣，这些方法、资源、技术和理论将显着推进进化研究。我们还发表了对基因组进化最新发展的平衡评论和前瞻性观点，提出了分子进化领域或应用的未来方向。

The journal "Molecular Biology and Evolution" focuses on the interface of molecular biology and evolutionary biology, publishing research in this area. We welcome manuscripts that address patterns, processes, and predictions across various levels, including population, taxonomy, function, and phenotype. In addition to fundamental findings with broad implications, we are also interested in publishing new and improved methods, resources, technologies, and theories that significantly advance evolutionary research. Furthermore, we publish balanced reviews and forward-looking perspectives on the latest developments in genome evolution, proposing future directions for the field of molecular evolution and its applications.

《Molecular Biology and Evolution》期刊专注于分子生物学与进化生物学的交叉领域，发表相关研究成果。我们欢迎涉及种群、分类、功能和表型等多个层面的模式、过程和预测的手稿。除了具有广泛影响的基础研究发现外，我们也对新的和改进的方法、资源、技术和理论感兴趣，这些内容将显著推动进化研究的发展。此外，我们还发表关于基因组进化最新进展的综合评论和前瞻性观点，探讨分子进化领域及其应用的未来方向。

Category	Quartile
生物学	1
生物学, 遗传学	1
生物学, 生化与分子生物学	2
生物学, 进化生物学	2

Dampened TLR2-mediated inflammatory signaling in bats

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Category	Quartile
GENETICS & HEREDITY	1