title: Reprogramming of myeloid angiogenic cells by Bartonella henselae leads to microenvironmental regulation of pathological angiogenesis.
abstract: The contribution of myeloid cells to tumour microenvironments is a decisive factor in cancer progression. Tumour-associated macrophages (TAMs) mediate tumour invasion and angiogenesis through matrix remodelling, immune modulation and release of pro-angiogenic cytokines. Nothing is known about how pathogenic bacteria affect myeloid cells in these processes. Here we show that Bartonella henselae, a bacterial pathogen causing vasculoproliferative diseases (bacillary angiomatosis), reprogrammes human myeloid angiogenic cells (MACs), a pro-angiogenic subset of circulating progenitor cells, towards a TAM-like phenotype with increased pro-angiogenic capacity. B. henselae infection resulted in inhibition of cell death, activation of angiogenic cellular programmes and induction of M2 macrophage polarization. MACs infected with B. henselae incorporated into endothelial sprouts and increased angiogenic growth. Infected MACs developed a vascular mimicry phenotype in vitro, and expression of B. henselae adhesin A was essential in inducing these angiogenic effects. Secretome analysis revealed that increased pro-angiogenic activities were associated with the creation of a tumour-like microenvironment dominated by angiogenic inflammatory cytokines and matrix remodelling compounds. Our results demonstrate that manipulation of myeloid cells by pathogenic bacteria can contribute to microenvironmental regulation of pathological tissue growth and suggest parallels underlying both bacterial infections and cancer.
authors: Institute for Medical Microbiology and Infection Control, Goethe University, Frankfurt am Main, Germany.
authors: Fiona
authors: F
authors: O'Rourke
authors: Institute for Medical Microbiology and Infection Control, Eberhard Karls University, Tübingen, Germany.
authors: Tanja
authors: T
authors: Mändle
authors: Institute for Cardiovascular Regeneration, Goethe University, Frankfurt am Main, Germany.
authors: Carmen
authors: C
authors: Urbich
authors: Institute for Cardiovascular Regeneration, Goethe University, Frankfurt am Main, Germany.
authors: Stefanie
authors: S
authors: Dimmeler
authors: Institute for Cardiovascular Physiology, Goethe University, Frankfurt am Main, Germany.
authors: U Ruth
authors: UR
authors: Michaelis
authors: Institute for Cardiovascular Physiology, Goethe University, Frankfurt am Main, Germany.
authors: Ralf P
authors: RP
authors: Brandes
authors: Department for Electronmicroscopy, Max Planck Institute for Developmental Biology, Tübingen, Germany.
authors: Matthias
authors: M
authors: Flötenmeyer
authors: Dr. Senckenberg Institute for Pathology, Goethe University, Frankfurt am Main, Germany.
authors: Claudia
authors: C
authors: Döring
authors: Dr. Senckenberg Institute for Pathology, Goethe University, Frankfurt am Main, Germany.
authors: Martin-Leo
authors: ML
authors: Hansmann
authors: Department of Radiation Oncology, Ludwig Maximilian University, Munich, Germany.
authors: Kirsten
authors: K
authors: Lauber
authors: Institute for Medical Microbiology and Infection Control, Goethe University, Frankfurt am Main, Germany.
authors: Wibke
authors: W
authors: Ballhorn
authors: Institute for Medical Microbiology and Infection Control, Goethe University, Frankfurt am Main, Germany.
authors: Volkhard A J
authors: VA
authors: Kempf
mesh_terms: D018416:Bartonella henselae / Q000502:physiology*; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000382:microbiology / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000382:microbiology / Q000502:physiology; D023461:Myeloid Progenitor Cells / Q000502:physiology*; D009389:Neovascularization, Pathologic