PT  - JOURNAL ARTICLE
AU  - Hysenaj Lisiena
AU  - De Laval Bérengère
AU  - Arce-Gorvel Vilma
AU  - Bosilkovski Mile
AU  - Gonzalez Gabriela
AU  - Debroas Guillaume
AU  - Sieweke Michael
AU  - Sarrazin Sandrine
AU  - Gorvel Jean-Pierre
TI  - CD150-dependent hematopoietic stem cells sensing of <em>Brucella</em> instructs myeloid commitment
AID  - 10.1101/2021.03.31.437872
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.31.437872
4099  - http://biorxiv.org/content/early/2021/04/01/2021.03.31.437872.short
4100  - http://biorxiv.org/content/early/2021/04/01/2021.03.31.437872.full
AB  - So far, hematopoietic stem cells (HSC) are considered the source of mature immune cells, the latter being the only ones capable of mounting an immune response. Recent evidence shows HSC can also directly sense cytokines released upon infection/inflammation and pathogen-associated molecular pattern interaction, while keeping a long-term memory of previous encountered signals. Direct sensing of danger signals by HSC induces early myeloid commitment, increases myeloid effector cell numbers and contributes to an efficient immune response. Here, using specific genetic tools on both host and pathogen sides, we show that HSC can directly sense B. abortus pathogenic bacteria within the bone marrow via the interaction of the cell surface protein CD150 with the bacterial outer membrane protein Omp25, inducing efficient functional commitment of HSC to the myeloid lineage. This is the first demonstration of a direct recognition of a live pathogen by HSC via CD150, which attests of a very early contribution of HSC to immune response.SUMMARY This work provides first evidence HSC directly sense Brucella abortus via the bacterial outer membrane protein Omp25 and the HSC surface receptor CD150, leading to functional commitment of HSC to myeloid lineage and very early initiation of immune response.Competing Interest StatementThe authors have declared no competing interest.