BARTONELLA HENSELAE MODULATES THE SECRETION OF CYTOKINES BY HUMAN MESENCHYMAL STROMAL CELLS

Introduction: Bartonella henselae causes different human diseases, the most prominent being cat scratch disease, a persistent, necrotizing lymphadenitis characterized by a typical granuloma that manifests in immunocompetent patients. Instead, in immunocompromized patients B. henselae can cause bacillary peliosis hepatis and bacillary angiomatosis. Endothelial cell infection represents an important step in the pathogenesis of cat scratch disease and bacillary angiomatosis. Experimental studies in a rat model showed that a brief bacteremia is followed by a 3-5-day bacteremia-free window before resurgence of persistent intraerythrocytic bacteremia that lasts for 8-11 weeks. This model highlights the possible existence of a sanctuary site where the initial infection gets established before persistent intraerythrocytic infection manifests. Mesenchymal stromal cells (MSC) are multipotent progenitor cells that can differentiate into various cell lineages such as osteocytes, condrocytes, and adipocytes, and have a proven ability to augment the neovascularization processes. Additionally, MSC also have antimicrobial proprieties and recently their role in the persistence of viable non replicating M. Tuberculosis has been established. The aim of this study was to determine the effect of B. henselae on the release of pro-angiogenic and pro-inflammatory cytokines by MSC, which could be possible candidates as reservoir cells. Materials and Methods: Human adipocyte-derived mesenchymal stromal cells (Ad-MSC) isolated from adipose tissue obtained by lipoaspiration from healthy donors were stimulated with different MOI of B. henselae for 24-96 hr. A B. henselae-conditioned medium (BCM) prepared after cultivation of bacteria for 24 hr in medium without antibiotics was used to stimulate MSC. Desferrioxamine was used as positive control of hypoxia induction. VEGF and IL-8 secretion upon B. henselae infection was measured by ELISA kits. Results: Infection of MSC with B. henselae resulted in an increase of VEGF and IL-8 secretion in a dose- and time-dependent manner. Moreover, the BCM increased the cytokine release in a dose-dependent manner. Discussion and Conclusions: Our results indicate that B. henselae induces the production of pro-angiogenic factors in MSC. The effect may be due to secretion of endothelial cell-stimulatory factor(s). These cells could represent a potential habitat of B. henselae trough their differentiation into cells with phenotypic and functional features of endothelial cells.