The Journal of Experimental Medicine
Fluorescence In Vivo Endomicroscopy
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© The Rockefeller University Press, 0022-1007/1999/10/1049/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 8, October 18, 1999 1049-1058

Immunoglobulin A1 Protease, an Exoenzyme of Pathogenic Neisseriae, Is a Potent Inducer of Proinflammatory Cytokines

Dirk R. Lorenzena, Frank Düxa, Uwe Wölka, Anastasios Tsirpouchtsidisa, Gaby Haasa, and Thomas F. Meyera
a Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, 10117 Berlin, Germany

Correspondence to: Thomas F. Meyer, Max-Planck-Institut für Infektionsbiologie, Abteilung Molekulare Biologie, Monbijoustr. 2, 10117 Berlin, Germany. Tel:49-30-2846-0400 Fax:49-30-2846-0401 E-mail:meyer{at}mpiib-berlin.mpg.de.

A characteristic of human pathogenic Neisseriae is the production and secretion of an immunoglobulin (Ig)A1-specific serine protease (IgA1 protease) that cleaves preferentially human IgA1 and other target proteins. Here we show a novel function for native IgA1 protease, i.e., the induction of proinflammatory cytokines such as tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-1ß, IL-6, and IL-8 from peripheral blood mononuclear cells. The capacity of IgA1 protease to elicit such cytokine responses in monocytes was enhanced in the presence of T lymphocytes. IgA1 protease did not induce the regulatory cytokine IL-10, which was, however, found in response to lipopolysaccharide and phytohemagglutinin. The immunomodulatory effects caused by IgA1 protease require a native form of the enzyme, and denaturation abolished cytokine induction. However, the proteolytic activity is not required for the cytokine induction by IgA1 protease. Our results indicate that IgA1 protease exhibits important immunostimulatory properties and may contribute substantially to the pathogenesis of neisserial infections by inducing large amounts of TNF-{alpha} and other proinflammatory cytokines. In particular, IgA1 protease may represent a key virulence determinant of bacterial meningitis.

Key Words: Neisseria gonorrhoeae, Neisseria meningitidis, inflammation, tumor necrosis, factor {alpha}, virulence factor


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