title: Coxiella burnetii stimulates production of RANTES and MCP-1 by mononuclear cells: modulation by adhesion to endothelial cells and its implication in Q fever.
abstract: Q fever is an infectious disease caused by Coxiella burnetii, which may become chronic when cytokine network and cell-mediated immune responses are altered. Chemokines, such as Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES, CCL5) and Monocyte Chemoattractant Protein-1 (MCP-1, CCL2), are specialized in the trafficing of peripheral blood mononuclear cells (PBMC), and are associated with T cell polarization that is essential for intracellular survival of C. burnetii. The present study investigated whether or not the infection status (no infection and acute or chronic infection with C. burnetii) of donors, affected the production of the two chemokines by PBMC with or without stimulation with virulent and avirulent C. burnetii. Our findings indicate that in vitro exposure to virulent or avirulent C. burnetii stimulated the production of RANTES and MCP-1 in PBMC obtained from healthy adults. The co-cultivation of endothelial cells and human PBMC resulted in an increased production of MCP-1 and the up-regulation of RANTES, which were contact-dependent. Unstimulated PBMC from patients with acute or chronic Q fever overproduced MCP-1. Interestingly, the addition of C. burnetii resulted in an increased production of RANTES and MCP-1 by PBMC obtained from patients with chronic Q fever, and the co-cultivation of PBMC with endothelial cells amplified increased production of chemokines. Circulating levels of RANTES and MCP-1 were also increased in chronic Q fever. We suggest that the overproduction of RANTES and MCP-1 secondary to the contact of PBMC with endothelium may perpetuate exaggerated inflammatory responses leading to inappropriate PBMC trafficking and to the pathogenesis of Q fever.
authors.affiliation: Unité des Rickettsies, CNRS UMR 6020, Université de la Méditerranée, Institut Fédératif de Recherche 48, Faculté de Médecine, 27 bd Jean Moulin, 13385 Marseille Cedex 5, France.
authors.forename: Soraya
authors.initials: S
authors.lastname: Meghari
authors.forename: Benoît
authors.initials: B
authors.lastname: Desnues
authors.forename: Christian
authors.initials: C
authors.lastname: Capo
authors.forename: Georges E
authors.initials: GE
authors.lastname: Grau
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mege
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002448:Cell Adhesion; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics*; D018946:Chemokine CCL5 / Q000097:blood / Q000235:genetics*; D018920:Coculture Techniques; D016997:Coxiella burnetii / Q000254:growth & development* / Q000472:pathogenicity; D042783:Endothelial Cells / Q000166:cytology / Q000382:microbiology; D005260:Female; D006801:Humans; D007118:Immunoassay; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D011778:Q Fever / Q000097:blood* / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014774:Virulence
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5