Smooth and rough lipopolysaccharide phenotypes of Brucella induce different intracellular trafficking and cytokine/chemokine release in human monocytes.
Virulence of the intracellular pathogen Brucella for humans is mainly associated with its lipopolysaccharide (LPS) phenotype, with smooth LPS phenotypes generally being virulent and rough ones not. The reason for this association is not quite understood. We now demonstrate by flow cytometry, electron microscopy, and ELISA that human peripheral blood monocytes interact both quantitatively and qualitatively different with smooth and rough Brucella organisms in vitro. We confirm that considerably higher numbers of rough than smooth brucellae attach to and enter the monocytes in nonopsonic conditions; but only smooth brucellae replicate in the host cells. We show for the first time that rough brucellae induce higher amounts than smooth brucellae of several CXC (GRO-alpha, IL-8) and CC (MIP-1alpha, MIP-1beta, MCP-1, RANTES) chemokines, as well as pro- (IL-6, TNF-alpha) and anti-inflammatory (IL-10) cytokines released by challenged monocytes. Upon uptake, phagosomes containing rough brucellae develop selective fusion competence to form spacious communal compartments, whereas phagosomes containing smooth brucellae are nonfusiogenic. Collectively, our data suggest that rough brucellae attract and infect monocytes more effectively than smooth brucellae, but only smooth LPS phenotypes establish a specific host cell compartment permitting successful parasitism. These novel findings link the LPS phenotype of Brucella and its virulence for humans at the level of the infected host cells. Whether this is due to a direct effect of the LPS molecules or to upstream bacterial mechanisms remains to be established.
Rittig
Michael G
MG
School of Biomedical Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, UK. michael.rittig@nottingham.ac.uk
Kaufmann
Andreas
A
Robins
Adrian
A
Shaw
Barry
B
Sprenger
Hans
H
Gemsa
Diethard
D
Foulongne
Vincent
V
Rouot
Bruno
B
Dornand
Jacques
J
D002002:Brucella / Q000502:physiology* / Q000648:ultrastructure; D002470:Cell Survival; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure; D010588:Phagosomes / Q000378:metabolism / Q000382:microbiology; D010641:Phenotype; D021381:Protein Transport
D018925:Chemokines; D016207:Cytokines; D008070:Lipopolysaccharides