CVI Accepts, published online ahead of print on 14 October 2009

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Clin. Vaccine Immunol. doi:10.1128/CVI.00310-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Veillonella parvula lipopolysaccharide: receptor recognition and immune intracellular pathways

Giovanni Matera, Valentina Muto, Maria Vinci, Emilia Zicca, Shahla Abdollahi-Roodsaz, Frank L. van de Veerdonk, Bart-Jan Kullberg, Maria Carla Liberto, Jos W.M. van der Meer, Alfredo Focà, Mihai G. Netea, and Leo A.B. Joosten^*

Institute of Microbiology, Department of Medical Sciences, University of Cantanzaro, Catanzaro, Italy; Department of Medicine, Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Rheumatology Research & Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

^* To whom correspondence should be addressed. Email: l.joosten{at}aig.umcn.nl.

Veillonella parvula is an anaerobic Gram-negative coccus that is part of the normal flora of animal and human mouth, gastrointestinal and genitourinary tract. Oral V. parvula is involved in the development of early periodontal disease as well as different type of serious infections. Present data on molecular mechanisms responsible for innate immune response against Veillonella are very scanty. The aim of this study was to investigate the Toll-like receptor pathways responsible for V. parvula LPS, and to identify the intracellular pathways induced by this recognition. V. parvula LPS stimulated TNF and IL-6 release in human PBMC in a dose-dependent manner. Pre-treatment of cells with a TLR4 antagonist significantly reduced TNF and IL-6 production in PBMC stimulated either with Veillonella or E. coli LPS. However, V. parvula LPS was 10 to 100 fold less active than E. coli LPS for cytokine induction. TNF, IL-1, IL-6 and IL-10 were released in wild-type and TLR 2-/-, but not in TLR4-/- mouse macrophage cultures. V. parvula LPS was able to activate the human PBMC p38 MAPK. A specific p38 MAPK inhibitor strongly inhibited V. parvula LPS-induced TNF, IL-1, IL-6 and IL-10. In conclusion, V. parvula LPS is able to induce cytokine production in both human and murine in vitro models, although it is less effective than enterobacteriaceae LPS. V. parvula LPS-stimulated cytokine induction, as well as p38 MAPK activation, are TLR4-dependent features.