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Infect. Immun. doi:10.1128/IAI.00951-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

MyD88 negatively controls hypergammaglobulinemia with autoantibody production during bacterial infection

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

^* To whom correspondence should be addressed. Email: Anne-Sophie.Korganow{at}hemato-ulp.u-strasbg.fr.

	Abstract

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 adaptator of the Toll/IL1 receptor signaling pathway, can actually acts as a negative regulator of B cell function in some settings. MyD88 deficient mice infected by Borrelia burgdorferi developped extreme hypergammaglobulinemia compared to wild-type animals, and high levels of 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 KO mice developed mostly IgM antibodies. Collectively, these data emphasize the complex role of the Toll/IL1 receptor pathway in tuning the immune response against infection and avoiding autoimmunity.