This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ehrchen, J. M.
Right arrow Articles by Spahn, T. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ehrchen, J. M.
Right arrow Articles by Spahn, T. W.

 Previous Article  |  Next Article 

Infection and Immunity, September 2008, p. 4241-4250, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.01714-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Absence of Cutaneous Lymph Nodes Results in a Th2 Response and Increased Susceptibility to Leishmania major Infection in Mice{triangledown}

Jan M. Ehrchen,1,2 Johannes Roth,1 Kirsten Roebrock,1 Georg Varga,2 Wolfram Domschke,3 Rodney Newberry,4 Clemens Sorg,1 Carsten Müller-Tidow,5 Cord Sunderkötter,2 Torsten Kucharzik,3 and Thomas W. Spahn3*

Institute of Immunology,1 Department of Dermatology,2 Department of Medicine B,3 Department of Medicine A, Münster University Hospital, 48149 Münster, Germany,5 Washington University of Medicine, Division of Gastroenterology, St. Louis, Missouri 631104

Received 21 December 2007/ Returned for modification 6 February 2008/ Accepted 12 June 2008

Lymph nodes (LNs) are important sentinel organs where antigen-presenting cells interact with T cells to induce adaptive immune responses. In cutaneous infection of mice with Leishmania major, resistance depends on the induction of a T-helper-cell-1 (Th1)-mediated cellular immune response in draining, peripheral LNs. We investigated whether draining, peripheral LNs are absolutely required for resistance against L. major infection. We investigated the course of experimental leishmaniasis in wild-type (wt) mice lacking peripheral LNs (pLNs), which we generated by in utero blockade of membrane-bound lymphotoxin, and in mice lacking pLNs or all LNs due to genetic deletion of lymphotoxin ligands or receptors. wt mice of the resistant C57BL/6 strain without local skin-draining LNs were still able to generate specific T-cell responses, but this yielded Th2 cells. This switch to a Th2 response resulted in severe systemic infection. We also confirmed these results with mice lacking pLNs due to genetic depletion of lymphotoxin-β. The complete absence of LNs due to a genetic depletion of the lymphotoxin-β receptor also resulted in a marked deterioration of disease and a Th2 response. Thus, in the absence of pLNs, an L. major-specific Th2 response is induced in the remaining secondary lymphoid organs, such as the spleen and non-skin-draining LNs. This indicates a critical requirement for pLNs to induce protective Th1 immunity and suggests that whether Th1 or Th2 priming to the same antigen occurs depends on the site of the primary antigen recognition.

* Corresponding author. Present address: Department of Internal Medicine and Gastroenterology, Marienhospital Osnabrück, Bischofsstrasse 1, D-49074 Osnabrueck, Germany. Phone: 49-541-326-4101. Fax: 49-541-326-4656. E-mail: thomas.spahn{at}mho.de

{triangledown} Published ahead of print on 14 July 2008.

Editor: W. A. Petri, Jr.

Infection and Immunity, September 2008, p. 4241-4250, Vol. 76, No. 9
0019-9567/08/$08.00+0     doi:10.1128/IAI.01714-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»