HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maurer, M. Articles by von Stebut, E. Search for Related Content PubMed PubMed Citation Articles by Maurer, M. Articles by von Stebut, E.

Skin mast cells control T cell-dependent host defense in Leishmania major infections

Marcus Maurer^*,, Susanna Lopez Kostka^*, Frank Siebenhaar^*,, Katharina Moelle^*, Martin Metz^*, Jürgen Knop^* and Esther von Stebut^*,1

^* Department of Dermatology, University Hospital Mainz, Mainz, Germany; and

Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, Berlin, Germany

¹Correspondence: Department of Dermatology, Johannes Gutenberg-University, Langenbeckstrasse 1, D-55131 Mainz, Germany. E-mail: vonstebu{at}mail.uni-mainz.de

Mast cells (MCs) initiate protective immunity against bacteria. Here we demonstrate that MCs also contribute to the control of parasitic skin infections by Leishmania major. L. major-infected MC-deficient Kit^W/Kit^W-v mice developed markedly larger skin lesions than did normal Kit+/+ mice (>2-fold), and cutaneous reconstitution with MCs resulted in normalization of lesion development. Kit^W/Kit^W-v lesions contained significantly more parasites, and infections resulted in enhanced spreading of parasites to the spleens as compared to controls. In addition, recruitment of proinflammatory neutrophils, macrophages, and dendritic cells (DCs) in infected mice was MC dependent. In the absence of MCs, reduced numbers of lesional DCs were associated with decreased production of Th1-promoting interleukin (IL)-12. Antigen-specific T cell priming was delayed in Kit^W/Kit^W-v mice and cytokine responses were skewed towards Th2. Notably, local skin MC reconstitution at sites of infection was sufficient for the induction of systemic protection. Thus, MC-mediated control of L. major infections is not limited to the induction of local inflammation. Instead, MCs contribute significantly to local DC recruitment, which mediates protective immunity. These findings extend the view of MCs as salient sentinels of innate immunity to complex host defense reactions against intracellular pathogens.—Maurer, M., Lopez Kostka, S., Siebenhaar, F., Moelle, K., Metz, M., Knop, J., von Stebut, E. Skin mast cells control T cell-dependent host defense in Leishmania major infections.

Key Words: leishmaniasis • Th1/Th2 • dendritic cell • cytokine release

This article has been cited by other articles:

				S. J. Jenkins, G. Perona-Wright, and A. S. MacDonald Full Development of Th2 Immunity Requires Both Innate and Adaptive Sources of CD154 J. Immunol., June 15, 2008; 180(12): 8083 - 8092. [Abstract] [Full Text] [PDF]

				T. Kambayashi, J. D. Baranski, R. G. Baker, T. Zou, E. J. Allenspach, J. E. Shoag, P. L. Jones, and G. A. Koretzky Indirect involvement of allergen-captured mast cells in antigen presentation Blood, February 1, 2008; 111(3): 1489 - 1496. [Abstract] [Full Text] [PDF]

				F. Siebenhaar, W. Syska, K. Weller, M. Magerl, T. Zuberbier, M. Metz, and M. Maurer Control of Pseudomonas aeruginosa Skin Infections in Mice Is Mast Cell-Dependent Am. J. Pathol., June 1, 2007; 170(6): 1910 - 1916. [Abstract] [Full Text] [PDF]