Journal Article

Evidence of Bacteroides fragilis Protection from Bartonella henselae-Induced Damage

Avallone, Bice, Infante, Teresa, Colicchio, Roberta, Ippolito, Rossana, Sommese, Linda, D'Armiento, Francesco Paolo, Costa, Valerio, Fiorito, Carmela, Pagliuca, Chiara, Casamassimi, Amelia, Cerciello, Raimondo, D'Armiento, Maria, Napoli, Claudio, Ciccodicola, Alfredo, Pastore, Gabiria, Salvatore, Paola, Scarpato, Margherita, Giovane, Alfonso

2012

Overview

Bartonella henselae is able to internalize endothelial progenitor cells (EPCs), which are resistant to the infection of other common pathogens. Bacteroides fragilis is a gram-negative anaerobe belonging to the gut microflora. It protects from experimental colitis induced by Helicobacter hepaticus through the polysaccharide A (PSA). The aim of our study was to establish: 1) whether B. fragilis colonization could protect from B. henselae infection; if this event may have beneficial effects on EPCs, vascular system and tissues. Our in vitro results establish for the first time that B. fragilis can internalize EPCs and competes with B. henselae during coinfection. We observed a marked activation of the inflammatory response by Real-time PCR and ELISA in coinfected cells compared to B. henselae-infected cells (63 vs 23 up-regulated genes), and after EPCs infection with mutant B. fragilis ΔPSA (≅90% up-regulated genes) compared to B. fragilis. Interestingly, in a mouse model of coinfection, morphological and ultrastructural analyses by hematoxylin-eosin staining and electron microscopy on murine tissues revealed that damages induced by B. henselae can be prevented in the coinfection with B. fragilis but not with its mutant B. fragilis ΔPSA. Moreover, immunohistochemistry analysis with anti-Bartonella showed that the number of positive cells per field decreased of at least 50% in the liver (20±4 vs 50±8), aorta (5±1 vs 10±2) and spleen (25±3 vs 40±6) sections of mice coinfected compared to mice infected only with B. henselae. This decrease was less evident in the coinfection with ΔPSA strain (35±6 in the liver, 5±1 in the aorta and 30±5 in the spleen). Finally, B. fragilis colonization was also able to restore the EPC decrease observed in mice infected with B. henselae (0.65 vs 0.06 media). Thus, our data establish that B. fragilis colonization is able to prevent B. henselae damages through PSA.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Angiomatosis, Bacillary - genetics / Angiomatosis, Bacillary - microbiology / Angiomatosis, Bacillary - pathology / Animal tissues / Animals / Antibiosis / Aorta / Bacteria / Bacteroides / Bacteroides fragilis / Bacteroides fragilis - physiology / Bacteroides Infections - genetics / Bacteroides Infections - microbiology / Bacteroides Infections - pathology / Bartonella / Bartonella henselae / Bartonella henselae - physiology / Biology / Biophysics / Cells (biology) / Cluster Analysis / Coinfection / Colitis / Colonization / Comorbidity / Cytokines - genetics / Damage prevention / Disease Models, Animal / Electron microscopy / Endothelial Cells - microbiology / Enzyme-linked immunosorbent assay / Female / Gene expression / Gene Expression Profiling / Genes / Health aspects / Host-Pathogen Interactions / Humans / Immune system / Immunoglobulins / Immunohistochemistry / Immunology / Infection / Infections / Inflammation / Inflammation - genetics / Inflammation - microbiology / Inflammatory response / Intestinal microflora / Laboratories / Liver / Lymphocytes B / Medicine / Mice / Microbiota (Symbiotic organisms) / Microflora / Microscopy / Pathogens / Pathology / Polysaccharides / Polysaccharides, Bacterial / Science / Spleen / Stem cells / Stem Cells - microbiology / Vascular system