Published online May 7, 2007
doi:10.1084/jem.20062013
The Journal of Experimental Medicine, Vol. 204, No. 5, 1107-1118
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Zhang et al.
Type I interferons protect neonates from acute inflammation through interleukin 10–producing B cells
Xiaoming Zhang1,2,3,
Edith Deriaud1,2,
Xinan Jiao3,
Deborah Braun4,
Claude Leclerc1,2, and
Richard Lo-Man1,2
1 Unité Régulation Immunitaire et Vaccinologie and 4 Immunobiologie des Cellules dendritiques, Institut Pasteur, 75724 Paris, Cedex 15, France
2 Institut National de la Santé et de la Recherche Médicale U883, 75724 Paris, France
3 Laboratory of Zoonosis and Immunology, Yangzhou University, 225009 Yangzhou, Jiangsu, China
CORRESPONDENCE R. Lo-Man: rloman{at}pasteur.fr
Newborns and infants are highly susceptible to viral and bacterial infections, but the underlying mechanism remains poorly understood. We show that neonatal B cells effectively control the production of proinflammatory cytokines by both neonatal plasmacytoid and conventional dendritic cells, in an interleukin (IL) 10–dependent manner, after Toll-like receptor (TLR) 9 triggering. This antiinflammatory property of neonatal B cells may extend to other TLR agonists (Pam3CSK4, lipopolysaccharide, and R848) and viruses. In the absence of B cells or of CD5+ B cell subsets, neonatal mice developed stronger inflammatory responses and became lethally susceptible to CpG challenge after galactosamine sensitization, whereas wild-type (WT) mice were resistant. Paradoxically, interferon (IFN)-
/ß enhanced the inflammatory response to CpG challenge in adult mice, whereas they helped to control neonatal acute inflammation by stimulating the secretion of IL-10 by neonatal B cells. Finally, WT neonatal B cells rescued IL-10–/– neonates from a lethal CpG challenge, whereas IFN-/ß receptor–deficient B cells did not. Our results show that type I IFNs support a negative regulatory role of neonatal B cells on TLR-mediated inflammation, with important implications for neonatal inflammation and infection.
Abbreviations used: AcNPV, Autographa californica nuclear polyhedrosis virus; cDC, conventional DC; Flt3L, Flt3 ligand; GalN, D-galactosamine; IFNAR–/–, type I IFN receptor deficient; IRF, IFN regulatory factor; µMT, B cell deficient; MyD88, myeloid differentiation factor 88; pDC, plasmacytoid DC; TLR, Toll-like receptor; TLR-L, TLR ligand.
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