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Infection and Immunity, December 2000, p. 6917-6923, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Gene Expression and Production of Tumor Necrosis Factor Alpha,
Interleukin-1
(IL-1
), IL-8, Macrophage Inflammatory Protein 1
(MIP-1
), MIP-1
, and Gamma Interferon-Inducible Protein 10 by
Human Neutrophils Stimulated with Group B Meningococcal Outer
Membrane Vesicles
José A.
Lapinet,1,2
Patrizia
Scapini,1
Federica
Calzetti,1
Oliver
Pérez,2 and
Marco A.
Cassatella1,*
Department of Pathology, Section of General
Pathology, University of Verona, 37134 Verona,
Italy,1 and Finlay Institute, 11600, Havana, Cuba2
Received 26 July 2000/Accepted 8 September 2000
Accumulation of polymorphonuclear neutrophils (PMN) into the
subarachnoidal space is one of the hallmarks of Neisseria
meningitidis infection. In this study, we evaluated the ability
of outer membrane vesicles (OMV) from N. meningitidis B to
stimulate cytokine production by neutrophils. We found that PMN
stimulated in vitro by OMV produce proinflammatory cytokines and
chemokines including tumor necrosis factor alpha (TNF-
),
interleukin-1
(IL-1
), IL-8, macrophage inflammatory protein 1
(MIP-1
), and MIP-1
. A considerable induction of gamma
interferon (IFN-
)-inducible protein 10 (IP-10) mRNA transcripts, as
well as extracellular IP-10 release, was also observed when neutrophils
were stimulated by OMV in combination with IFN-
. Furthermore, PMN
stimulated by OMV in the presence of IFN-
demonstrated an
enhanced capacity to release TNF-
, IL-1
, IL-8, and MIP-1
compared to stimulation with OMV alone. In line with its
downregulatory effects on neutrophil-derived proinflammatory cytokines, IL-10 potently inhibited TNF-
, IL-1
, IL-8, and
MIP-1
production triggered by OMV. Finally, a neutralizing
anti-TNF-
monoclonal antibody (MAb) did not influence the release of
IL-8 and MIP-1
induced by OMV, therefore excluding a role
for endogenous TNF-
in mediating the induction of chemokine
release by OMV. In contrast, the ability of lipopolysaccharide from
N. meningitidis B to induce the production of IL-8 and
MIP-1
was significantly inhibited by anti-TNF-
MAb. Our results
establish that, in response to OMV, neutrophils produce a
proinflammatory profile of cytokines and chemokines which may not only
play a role in the pathogenesis of meningitis but may also contribute
to the development of protective immunity to serogroup B meningococci.
*
Corresponding author. Mailing address: Department of
Pathology, Section of General Pathology, Strada Le Grazie 4, I-37134 Verona, Italy. Phone: 39-045-8027130. Fax: 39-045-8027127. E-mail: MCNCSS{at}borgoroma.univr.it.
Infection and Immunity, December 2000, p. 6917-6923, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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