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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Woods, A.
Right arrow Articles by Martin, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Woods, A.
Right arrow Articles by Martin, T.

 Previous Article  |  Next Article 

Infection and Immunity, April 2008, p. 1657-1667, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.00951-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

MyD88 Negatively Controls Hypergammaglobulinemia with Autoantibody Production during Bacterial Infection{triangledown}

Anne Woods,1 Pauline Soulas-Sprauel,1 Benoit Jaulhac,3 Bérénice Arditi,1 Anne-Marie Knapp,1 Jean-Louis Pasquali,1,2 Anne-Sophie Korganow,1,2* and Thierry Martin1,2

Institut National de la Santé et de la Recherche Médicale, U737, Strasbourg 67000, France,1 Université Louis Pasteur, Faculté de Médecine, Hôpital Civil, Strasbourg 67000, France,2 Université Louis Pasteur, Bactériologie, Hôpital Civil, Strasbourg 67000, France3

Received 12 July 2007/ Returned for modification 20 August 2007/ Accepted 14 January 2008

A large body of evidence has convincingly shown that Toll-like receptors are necessary sensors for infections with pathogens, but their activation was also suggested to generate autoimmunity. During experimental infections, the lack of these sensors or of their signaling molecules should lead to a deficient immune response. We found out that MyD88, the major adaptor of the Toll/interleukin-1 (Toll/IL-1) receptor signaling pathway, can actually act as a negative regulator of B-cell function in some settings. MyD88-deficient mice infected by Borrelia burgdorferi developed extreme hypergammaglobulinemia compared to wild-type animals, with high levels of immunoglobulin M (IgM) autoantibodies. In vivo, cell transfer experiments and cell blocking assays showed that this phenotype was not linked to the absence of MyD88 in B cells but rather to CD4 T-cell and likely dendritic cell dysfunctions leading to a Th1-to-Th2 cytokine switch. In addition, our results suggest a relative defect in the Ig class switch recombination process, since MyD88 knockout mice developed mostly IgM antibodies. Collectively, these data emphasize the complex role of the Toll/IL-1 receptor pathway in tuning the immune response against infection and avoiding autoimmunity.

* Corresponding author. Mailing address: INSERM U737, Hôpital Civil, Strasbourg 67000, France. Phone: 333 88 15 53 50. Fax: 333 88 11 64 64. E-mail: Anne-Sophie.Korganow{at}hemato-ulp.u-strasbg.fr

{triangledown} Published ahead of print on 28 January 2008.

Editor: B. A. McCormick

Infection and Immunity, April 2008, p. 1657-1667, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.00951-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Malkiel, S., Kuhlow, C. J., Mena, P., Benach, J. L. (2009). The Loss and Gain of Marginal Zone and Peritoneal B Cells Is Different in Response to Relapsing Fever and Lyme Disease Borrelia. J. Immunol. 182: 498-506 [Abstract] [Full Text]  


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