The mannose receptor on sinusoidal lining cells mediates two-step bacterial clearance in the human spleen
Abstract
Abstract The human spleen plays a critical role in clearing bacteria from the bloodstream, particularly during septicaemia; yet the cellular mechanisms underlying this function remain poorly defined. Using a dual translational approach including ex vivo perfusion of human spleens and splenic primary cell cultures, we identify a previously unrecognised division of tasks in splenic antibacterial defence. In the human splenic red pulp, sinusoidal lining cells capture and retain bacteria via the CD206 mannose receptor. Subsequently, the bactericidal activity by red pulp macrophages involves the scavenger receptor MARCO. This two-step process ensures efficient removal of encapsulated pathogens as inhibition of CD206 receptor impacted not only Streptococcus pneumoniae killing, independent of the capsular serotype, but also on Klebsiella pneumoniae and Escherichia coli revising the mechanism of pathogen clearance in the human spleen. Trial registration: REC 18/EM/0057 (NCT04620824) and CE: 668/2023/Sper/AOU.
Article Details
Authors (32)
Neama Alnabati
Francesco Flandi
Tareq Al Saoudi
Giulia Cattabriga
Talia Richardson
Alessia Gennai
Daniele Ghezzi
Ryan G. Hames
John Isherwood
Trisha Kanani
Zydrune Jasiunaite
Shiying Tang
Giuliana Germinario
Giorgia Radi
Francesca Rizzo
Katrin Schilcher
Christopher D. Bayliss
Romina Camilli
Marco Caprini
Carola Parolin
Stefano Fedi
Wen Y. Chung
Giuseppe Garcea
Enrico Giampieri
Gastone Castellani
Kornelis Straatman
Stefano Bruno
Claudia Trappetti
Matteo Ravaioli
Ashley R. Dennison
Luisa Martinez-Pomares
Marco R. Oggioni