Dectin-1 recognizes bacterial EF-Tu during infection

ABSTRACT: Dectin-1 (CLEC7A) is a pattern-recognition receptor known for its essential role in antifungal defense, and may also be associated with antibacterial immunity. Here we show that in murine pneumonia models, Dectin-1 deficiency impaired pulmonary clearance of Streptococcus pneu-moniae and Haemophilus influenzae. This susceptibility was gene-dose-dependent, with hetero-zygous (Clec7a+/–) and knockout (Clec7a–/–) mice exhibiting higher bacterial burdens and al-tered immune responses compared to wild-type mice. Translating these findings to humans, analysis of 28,175 genome-sequenced individuals showed that the loss-of-function CLEC7A variant Y238X (rs16910526) was associated with increased risk of bacterial pneumonia. Affini-ty purification followed by mass spectrometry identified bacterial elongation factor Tu (EF-Tu) as a conserved Dectin-1 ligand. EF-Tu bound the Dectin-1 carbohydrate-recognition domain and, when clustered, activated downstream NF-κB signaling. These findings establish EF-Tu as a pathogen-associated molecular pattern and define Dectin-1 as an innate receptor controlling antibacterial inflammation and host susceptibility to pneumonia.

INSTRUMENT(S):

ORGANISM(S): Haemophilus Influenzae 2019

SUBMITTER: Carsten Scavenius  

LAB HEAD: Carsten Scavenius

PROVIDER: PXD070889 | Pride | 2026-09-11

REPOSITORIES: Pride