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Infection and Immunity, December 2004, p. 6978-6986, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6978-6986.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Mycoplasma-Derived Macrophage-Activating 2-Kilodalton Lipopeptide Triggers Global Immune Activation on Nasal Mucosa-Associated Lymphoid Tissues

Faiza Rharbaoui,1 Astrid Westendorf,2 Claudia Link,1 Sandra Felk,1 Jan Buer,2 Matthias Gunzer,3 and Carlos A. Guzmán1*

Vaccine Research Group,1 Mucosal Immunity Research Group,2 Immunodynamic Research Group, German Research Center for Biotechnology, Braunschweig, Germany3

Received 21 June 2004/ Returned for modification 4 August 2004/ Accepted 20 August 2004

A better knowledge on how immune responses are initiated in mucosal tissues would facilitate the design of new mucosal vaccines, as well as improve our understanding on host defense against infection. We investigated the mechanisms of adjuvanticity of the Mycoplasma-derived macrophage-activating 2-kDa lipopeptide (MALP-2), which binds to the heterodimer formed by the Toll-like receptors 2 and 6 (TLR2 and -6), at the level of the murine nasal mucosa-associated lymphoid tissues (NALT). TLR2 expression analysis demonstrated that several cell types from the nasal cavity were able to overexpress this receptor, either constitutively (such as B cells) or after stimulation (i.e., T cells). MALP-2 stimulated a strong B-cell activation. In addition, the antigen presentation capacity of dendritic cells was improved after in vivo loading with antigen in the presence of MALP-2. We also observed an up-regulated expression of activation markers and adhesion molecules on T cells, suggesting that they have enhanced responsiveness and interaction potential. Quantitative reverse transcription-PCR analysis showed that MALP-2 administration resulted in the stimulation of a proinflammatory cascade. We observed an early up-regulated expression of IP-10, MCP-1, MCP-3, MIP-1{alpha}, MIP-2, and CCR-2 which was reversed within 36 h. The obtained results demonstrated that MALP-2 creates a reversible local microenvironment which promotes effective priming of T and B cells in the NALT.

* Corresponding author. Mailing address: Vaccine Research Group, Division of Microbiology, GBF German Research Center for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany. Phone: 49-531-6181558. Fax: 49-531-6181411. E-mail: cag{at}gbf.de.

Editor: D. L. Burns

Infection and Immunity, December 2004, p. 6978-6986, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6978-6986.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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