1. Academic Validation
  2. Bartonella henselae Persistence within Mesenchymal Stromal Cells Enhances Endothelial Cell Activation and Infectibility That Amplifies the Angiogenic Process

Bartonella henselae Persistence within Mesenchymal Stromal Cells Enhances Endothelial Cell Activation and Infectibility That Amplifies the Angiogenic Process

  • Infect Immun. 2021 Jul 15;89(8):e0014121. doi: 10.1128/IAI.00141-21.
Sara Scutera  # 1 Stefania Mitola  # 2 Rosaria Sparti 1 Valentina Salvi 2 Elisabetta Grillo 2 Giorgia Piersigilli 1 Mattia Bugatti 2 Daniela Alotto 3 Tiziana Schioppa 2 4 Silvano Sozzani  # 5 Tiziana Musso  # 1


  • 1 Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy.
  • 2 Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
  • 3 Skin Bank, Department of General and Specialized Surgery, A.O.U. Città della Salute e della Scienza, Turin, Italy.
  • 4 Humanitas Clinical and Research Center, IRCCS Rozzano, Milan, Italy.
  • 5 Laboratory affiliated with Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
  • # Contributed equally.

Some Bacterial pathogens can manipulate the angiogenic response, suppressing or inducing it for their own ends. In humans, Bartonella henselae is associated with cat-scratch disease and vasculoproliferative disorders such as bacillary angiomatosis and bacillary peliosis. Although endothelial cells (ECs) support the pathogenesis of B. henselae, the mechanisms by which B. henselae induces EC activation are not completely clear, as well as the possible contributions of other cells recruited at the site of Infection. Mesenchymal stromal cells (MSCs) are endowed with angiogenic potential and play a dual role in infections, exerting antimicrobial properties but also acting as a shelter for pathogens. Here, we delved into the role of MSCs as a reservoir of B. henselae and modulator of EC functions. B. henselae readily infected MSCs and survived in perinuclearly bound vacuoles for up to 8 days. Infection enhanced MSC proliferation and the expression of epidermal growth factor receptor (EGFR), Toll-like Receptor 2 (TLR2), and nucleotide-binding oligomerization domain-containing protein 1 (NOD1), proteins that are involved in Bacterial internalization and cytokine production. Secretome analysis revealed that infected MSCs secreted higher levels of the proangiogenic factors vascular endothelial growth factor (VEGF), Fibroblast Growth Factor 7 (FGF-7), matrix metallopeptidase 9 (MMP-9), placental growth factor (PIGF), serpin E1, thrombospondin 1 (TSP-1), urokinase-type plasminogen activator (uPA), interleukin 6 (IL-6), platelet-derived growth Factor D (PDGF-D), chemokine ligand 5 (CCL5), and C-X-C motif chemokine ligand 8 (CXCL8). Supernatants from B. henselae-infected MSCs increased the susceptibility of ECs to B. henselae Infection and enhanced EC proliferation, invasion, and reorganization in tube-like structures. Altogether, these results indicate MSCs as a still underestimated niche for persistent B. henselae Infection and reveal MSC-EC cross talk that may contribute to exacerbate bacterium-induced angiogenesis and granuloma formation.


Bartonella henselae; CXCL8; EGFR; NOD; TLR; VEGF; angiogenesis; mesenchymal stromal cells.