(The FASEB Journal. 2008;22:lb477)
© 2008 FASEB
Probiotics protect (NZBxNZW)F1 mice against lupus by a mechanism involving IL-10 production by dendritic cells and regulatory cells
Jean N. Manirarora,
Sarah A. Parnell,
Safinur Atay,
Michele M. Kosiewicz and
Pascale Alard
Microbiology & Immunology, University of Louisville, Louisville, KY
ABSTRACT
The lack of exposure to infectious agents in industrialized countries may compromise the development of effective immunoregulation. Microorganisms can evade the immune response via induction of tolerogenic APC and regulatory cells, and have been shown to prevent the development of autoimmune diseases. Probiotics, including Lactobacilli, from the normal flora play an important role in the immune system development. The goal of this study was to test whether probiotics prevent lupus development in (NZBxNZW)F1 mice and identify the mechanisms mediating protection. We have found that feeding Lactobacilli could delay lupus onset and severity. This protection was associated with an increase in the percentage of CD4+Foxp3+ cells and APC expressing B7-1 and B7-2 in the lymphoid organs, and production of high levels of IL-10 by T cells upon stimulation in vitro. Moreover, bone marrow-derived DC (BM-DC) stimulated with Lactobacilli also produced copious amounts of IL-10, and when transferred into (NZBxNZW)F1 mice delayed lupus onset and severity. In addition, significant increases in IL-10 levels were detected in most of the sera from mice injected with Lactobacilli-treated BM-DC. Altogether these data suggest that IL-10 may play a significant role in probiotic-mediated protection against lupus either directly, by suppressing pro-inflammatory responses, and/or by inducing regulatory cells. Supported by LRI.
