Some bacterial pathogens can manipulate the angiogenic response, suppressing or inducing it for their own ends. In humans,
B. 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
Bartonella
, the mechanisms by which
Bartonella
induces EC activation are not completely clear, as well as the possible contribution 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 reservoir of
Bartonella
and modulator of EC functions.
B. henselae
readily infected MSCs and survived in perinuclear bound vacuoles for up to 8 days. Infection enhanced MSC proliferation and the expression of EGFR, TLR2 and NOD1, proteins that are involved in bacterial internalization and cytokine production. Secretome analysis revealed that infected MSCs secreted higher levels of the proangiogenic factors VEGF, FGF-7, MMP-9, PIGF, serpin E1, TSP-1, uPA, IL-6, PDGF-D, CCL5 and 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 candidate MSCs as a still underestimated niche for
B. henselae
persistent infection and reveal a MSC-EC crosstalk that may contribute to exacerbate bacterial-induced angiogenesis and granuloma formation.