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Infection and Immunity, January 2007, p. 175-183, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01385-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Microbial Metalloproteinases Mediate Sensing of Invading Pathogens and Activate Innate Immune Responses in the Lepidopteran Model Host Galleria mellonella{triangledown}

Boran Altincicek,1 Monica Linder,2 Dietmar Linder,2 Klaus T. Preissner,2 and Andreas Vilcinskas1*

Institute of Phytopathology and Applied Zoology,1 Institute of Biochemistry, Justus Liebig University of Giessen, 35392 Giessen, Germany2

Received 29 August 2006/ Returned for modification 7 October 2006/ Accepted 23 October 2006

Thermolysin-like metalloproteinases such as aureolysin, pseudolysin, and bacillolysin represent virulence factors of diverse bacterial pathogens. Recently, we discovered that injection of thermolysin into larvae of the greater wax moth, Galleria mellonella, mediated strong immune responses. Thermolysin-mediated proteolysis of hemolymph proteins yielded a variety of small-sized (<3 kDa) protein fragments (protfrags) that are potent elicitors of innate immune responses. In this study, we report the activation of a serine proteinase cascade by thermolysin, as described for bacterial lipopolysaccharides (LPS), that results in subsequent prophenoloxidase activation leading to melanization, an elementary immune defense reaction of insects. Quantitative real-time reverse transcription-PCR analyses of the expression of immune-related genes encoding the inducible metalloproteinase inhibitor, gallerimycin, and lysozyme demonstrated increased transcriptional rates after challenge with purified protfrags similar to rates after challenge with LPS. Additionally, we determined the induction of a similar spectrum of immune-responsive proteins that were secreted into the hemolymph by using comparative proteomic analyses of hemolymph proteins from untreated larvae and from larvae that were challenged with either protfrags or LPS. Since G. mellonella was recently established as a valuable pathogenicity model for Cryptococcus neoformans infection, the present results add to our understanding of the mechanisms of immune responses in G. mellonella. The obtained results support the proposed danger model, which suggests that the immune system senses endogenous alarm signals during infection besides recognition of microbial pattern molecules.

* Corresponding author. Mailing address: Institute of Phytopathology and Applied Zoology, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26-32, 35392 Giessen, Germany. Phone: 49 641 99 37600. Fax: 49 641 99 37609. E-mail: Andreas.Vilcinskas{at}agrar.uni-giessen.de.

{triangledown} Published ahead of print on 30 October 2006.

Editor: A. Camilli

Infection and Immunity, January 2007, p. 175-183, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01385-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Altincicek, B., Stotzel, S., Wygrecka, M., Preissner, K. T., Vilcinskas, A. (2008). Host-Derived Extracellular Nucleic Acids Enhance Innate Immune Responses, Induce Coagulation, and Prolong Survival upon Infection in Insects. J. Immunol. 181: 2705-2712 [Abstract] [Full Text]  


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