Abstract
Abstract: The key importance of the cellular innate immunity in controlling invasive infection has been known for decades, but there is a dramatic lack of functional information on the events which take place in tissue macrophages within the human spleen upon microbial infection. To explore early events in the human spleen, we aimed to dissect interactions of tissue macrophages with encapsulated bacterial pathogens during ex vivo organ perfusion. Data have elucidated a unique two-step mechanism by which the human spleen captures, and the clears capsulated bacterial pathogen. This work has revolutionised understanding of clearance of blood born pathogens with profound implications for prevention and treatment of systemic bacterial infection.
Results achieved
: The human spleen plays a critical role in clearing bacteria from the bloodstream, particularly during septicaemia; however, the cellular mechanisms underlying this function remain poorly understood. With a interdisciplinary team and using a dual translational approach combining ex vivo perfusion of human spleens with primary splenic cell cultures, we identified a previously unrecognised division of labour in splenic antibacterial defence. In the human splenic red pulp, sinusoidal lining cells capture and retain bacteria through the CD206 mannose receptor. Subsequently, red pulp macrophages mediate bacterial killing via the scavenger receptor MARCO (Macrophage Receptor with Collagenous structure). This two-step process ensures efficient elimination of encapsulated pathogens, as inhibition of CD206 impaired the killing of Streptococcus pneumoniae independently of capsular serotype, as well as that of Klebsiella pneumoniae and Escherichia coli. These findings revise the current understanding of pathogen clearance in the human spleen and reveal distinct, cooperative cellular mechanisms underlying splenic antibacterial immunity. This work was published on Nature Communications in 2026 (doi: 10.1038/s41467-026-72430-8). References and data sharing: • Alnabati N, Flandi F, Al Saoudi T, Cattabriga G, Richardson T, Gennai A, Ghezzi D, Hames RG, Isherwood J, Kanani T, Jasiunaite Z, Tang S, Germinario G, Radi G, Rizzo F, Schilcher K, Bayliss CD, Camilli R, Caprini M, Parolin C, Fedi S, Chung WY, Garcea G, Giampieri E, Castellani G, Straatman K, Bruno S, Trappetti C, Ravaioli M, Dennison AR, Martinez-Pomares L, Oggioni MR. The mannose receptor on sinusoidal lining cells mediates two-step bacterial clearance in the human spleen. Nat Commun. 2026 Apr 29. doi: 10.1038/s41467-026-72430-8. Epub ahead of print. PMID: 42056114. • Flandi, Francesco ; Oggioni, Marco Rinaldo (2026) Data relative to histology analyses from the publication “The Mannose Receptor on Sinusoidal Lining Cells Mediates Two-Step Bacterial Clearance in the Human Spleen". University of Bologna. DOI 10.6092/unibo/amsacta/8855. [Dataset] • Flandi, Francesco ; Ravaioli, Matteo ; Oggioni, Marco Rinaldo (2026) Timelapse microscopy dataset - The Mannose Receptor on Sinusoidal Lining Cells Mediates Two-Step Bacterial Clearance in the Human Spleen. University of Bologna. DOI 10.6092/unibo/amsacta/8725. [Dataset]Dettagli del progetto
Responsabile scientifico: Marco Rinaldo Oggioni
Strutture Unibo coinvolte:
Dipartimento di Farmacia e Biotecnologie
Coordinatore:
ALMA MATER STUDIORUM - Università di Bologna(Italy)
Contributo totale di progetto: Euro (EUR) 239.297,00
Contributo totale Unibo: Euro (EUR) 135.552,00
Durata del progetto in mesi: 24
Data di inizio
30/11/2023
Data di fine:
28/02/2026
