Type I interferons protect neonates from acute inflammation through interleukin 10-producing B cells.
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)-alpha/beta 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-alpha/beta 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.
Zhang
Xiaoming
X
Unité Régulation Immunitaire et Vaccinologie and 4Immunobiologie des Cellules Dendritiques, Institut Pasteur, Paris, Cedex 15, France.
Deriaud
Edith
E
Jiao
Xinan
X
Braun
Deborah
D
Leclerc
Claude
C
Lo-Man
Richard
R
D019264:Adoptive Transfer; D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D007249:Inflammation / Q000276:immunology*; D007370:Interferon Type I / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051217:Toll-Like Receptor 9 / Q000378:metabolism
D007370:Interferon Type I; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D016753:Interleukin-10