CoChat
Sign Up
Cited by 150Immune Response and InflammationT-cell and B-cell Immunologyinterferon and immune responses

Type I interferons protect neonates from acute inflammation through interleukin 10–producing B cells

Open access
Zhang, Xiaoming, Deriaud, Edith, Jiao, Xinan, Braun, Deborah, Leclerc, Claude, Lo-Man, Richard·2007·The Journal of Experimental Medicine
DOI 10.1084/jem.20062013PMC PMC2118587
Open this paper in CoChat — free account

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1084/jem.20062013

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • B1 B cells are important producers of IL-10 after innate immune activation and are crucial in controlling lethal TLR-mediated inflammation by dampening excessive inflammation in an IL-10-dependent manner.

    “In addition, B1 B cells are important producers of IL-10 after innate immune activation and are crucial in controlling lethal Toll-Like Re­ ceptor (TLR)-mediated inflammation by dampening excessive inflam­ mation in an IL-10-dependent manner [47,48].”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [47]

    The Results sections report that neonatal CD5+CD23− B cells produce IL-10 after TLR stimulation and that their IL-10 protects neonatal mice from lethal CpG-induced inflammation. The claim extends this finding to B1 B cells generally, whereas the demonstrated protection is specific to neonatal mice and the CD5+CD23− subset. The supplied passages do not give page numbers. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 51

  1. [1]Siegrist, C.A. 2001. Neonatal and early life vaccinology. Vaccine. 19: 3331–3346. 11348697
  2. [2]Adkins, B., C. Leclerc, and S. Marshall-Clarke. 2004. Neonatal adaptive immunity comes of age. Nat. Rev. Immunol. 4: 553–564. 15229474
  3. [3]Akira, S., S. Uematsu, and O. Takeuchi. 2006. Pathogen recognition and innate immunity. Cell. 124: 783–801. 16497588
  4. [4]Iwasaki, A., and R. Medzhitov. 2004. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5: 987–995. 15454922
  5. [6]Lee, S.M., Y. Suen, L. Chang, V. Bruner, J. Qian, J. Indes, E. Knoppel, C. van de Ven, and M.S. Cairo. 1996. Decreased interleukin-12 (IL-12) from activated cord versus adult peripheral blood mononuclear cells and upregulation of interferon-gamma, natural killer, and lymphokine-activated killer activity by IL-12 in cord blood mononuclear cells. Blood. 88: 945–954. 8704253
  6. [7]Levy, O. 2005. Innate immunity of the human newborn: distinct cytokine responses to LPS and other Toll-like receptor agonists. J. Endotoxin Res. 11: 113–116. 15949138
  7. [8]Upham, J.W., P.T. Lee, B.J. Holt, T. Heaton, S.L. Prescott, M.J. Sharp, P.D. Sly, and P.G. Holt. 2002. Development of interleukin-12-producing capacity throughout childhood. Infect. Immun. 70: 6583–6588. 12438328 PMC133015
  8. [9]Goriely, S., B. Vincart, P. Stordeur, J. Vekemans, F. Willems, M. Goldman, and D. De Wit. 2001. Deficient IL-12(p35) gene expression by dendritic cells derived from neonatal monocytes. J. Immunol. 166: 2141–2146. 11160266
  9. [10]Jiang, H., C. Van De Ven, P. Satwani, L.V. Baxi, and M.S. Cairo. 2004. Differential gene expression patterns by oligonucleotide microarray of basal versus lipopolysaccharide-activated monocytes from cord blood versus adult peripheral blood. J. Immunol. 172: 5870–5879. 15128766
  10. [11]Karlsson, H., C. Hessle, and A. Rudin. 2002. Innate immune responses of human neonatal cells to bacteria from the normal gastrointestinal flora. Infect. Immun. 70: 6688–6696. 12438343 PMC133091
  11. [12]Sun, C.M., L. Fiette, M. Tanguy, C. Leclerc, and R. Lo-Man. 2003. Ontogeny and innate properties of neonatal dendritic cells. Blood. 102: 585–591. 12663436
  12. [13]Dakic, A., Q.X. Shao, A. D'Amico, M. O'Keeffe, W.F. Chen, K. Shortman, and L. Wu. 2004. Development of the dendritic cell system during mouse ontogeny. J. Immunol. 172: 1018–1027. 14707075
  13. [14]Sun, C.M., E. Deriaud, C. Leclerc, and R. Lo-Man. 2005. Upon TLR9 signaling, CD5+ B cells control the IL-12-dependent Th1-priming capacity of neonatal DCs. Immunity. 22: 467–477. 15845451
  14. [15]Levy, O., K.A. Zarember, R.M. Roy, C. Cywes, P.J. Godowski, and M.R. Wessels. 2004. Selective impairment of TLR-mediated innate immunity in human newborns: neonatal blood plasma reduces monocyte TNF-alpha induction by bacterial lipopeptides, lipopolysaccharide, and imiquimod, but preserves the response to R-848. J. Immunol. 173: 4627–4634. 15383597
  15. [16]Berland, R., and H.H. Wortis. 2002. Origins and functions of B-1 cells with notes on the role of CD5. Annu. Rev. Immunol. 20: 253–300. 11861604
  16. [17]Montecino-Rodriguez, E., H. Leathers, and K. Dorshkind. 2006. Identification of a B-1 B cell-specified progenitor. Nat. Immunol. 7: 293–301. 16429139
  17. [18]Vosshenrich, C.A., A. Cumano, W. Muller, J.P. Di Santo, and P. Vieira. 2003. Thymic stromal-derived lymphopoietin distinguishes fetal from adult B cell development. Nat. Immunol. 4: 773–779. 12872121
  18. [19]Vosshenrich, C.A., A. Cumano, W. Muller, J.P. Di Santo, and P. Vieira. 2004. Pre-B cell receptor expression is necessary for thymic stromal lymphopoietin responsiveness in the bone marrow but not in the liver environment. Proc. Natl. Acad. Sci. USA. 101: 11070–11075. 15263090 PMC503742
  19. [20]Briles, D.E., M. Nahm, K. Schroer, J. Davie, P. Baker, J. Kearney, and R. Barletta. 1981. Antiphosphocholine antibodies found in normal mouse serum are protective against intravenous infection with type 3 Streptococcus pneumoniae. J. Exp. Med. 153: 694–705. 7252411 PMC2186108
  20. [21]Baumgarth, N., O.C. Herman, G.C. Jager, L.E. Brown, L.A. Herzenberg, and J. Chen. 2000. B-1 and B-2 cell–derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection. J. Exp. Med. 192: 271–280. 10899913 PMC2193249
  21. [22]Martin, F., A.M. Oliver, and J.F. Kearney. 2001. Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity. 14: 617–629. 11371363
  22. [23]O'Garra, A., R. Chang, N. Go, R. Hastings, G. Haughton, and M. Howard. 1992. Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10. Eur. J. Immunol. 22: 711–717. 1547817
  23. [24]Duramad, O., K.L. Fearon, J.H. Chan, H. Kanzler, J.D. Marshall, R.L. Coffman, and F.J. Barrat. 2003. IL-10 regulates plasmacytoid dendritic cell response to CpG-containing immunostimulatory sequences. Blood. 102: 4487–4492. 12946990
  24. [25]Abe, T., H. Hemmi, H. Miyamoto, K. Moriishi, S. Tamura, H. Takaku, S. Akira, and Y. Matsuura. 2005. Involvement of the Toll-like receptor 9 signaling pathway in the induction of innate immunity by baculovirus. J. Virol. 79: 2847–2858. 15709004 PMC548444
  25. [27]Hayakawa, K., R.R. Hardy, D.R. Parks, and L.A. Herzenberg. 1983. The “Ly-1 B” cell subpopulation in normal immunodefective, and autoimmune mice. J. Exp. Med. 157: 202–218. 6600267 PMC2186909
  26. [28]Galanos, C., M.A. Freudenberg, and W. Reutter. 1979. Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc. Natl. Acad. Sci. USA. 76: 5939–5943. 293694 PMC411768
  27. [29]Vollstedt, S., M. Franchini, H.P. Hefti, B. Odermatt, M. O'Keeffe, G. Alber, B. Glanzmann, M. Riesen, M. Ackermann, and M. Suter. 2003. Flt3 ligand-treated neonatal mice have increased innate immunity against intracellular pathogens and efficiently control virus infections. J. Exp. Med. 197: 575–584. 12615899 PMC2193820
  28. [30]Genovese, F., G. Mancuso, M. Cuzzola, C. Biondo, C. Beninati, D. Delfino, and G. Teti. 1999. Role of IL-10 in a neonatal mouse listeriosis model. J. Immunol. 163: 2777–2782. 10453021
  29. [31]Ito, S., K.J. Ishii, M. Gursel, H. Shirotra, A. Ihata, and D.M. Klinman. 2005. CpG oligodeoxynucleotides enhance neonatal resistance to Listeria infection. J. Immunol. 174: 777–782. 15634898
  30. [32]Arulanandam, B.P., J.N. Mittler, W.T. Lee, M. O'Toole, and D.W. Metzger. 2000. Neonatal administration of IL-12 enhances the protective efficacy of antiviral vaccines. J. Immunol. 164: 3698–3704. 10725728
  31. [33]Mancuso, G., V. Cusumano, F. Genovese, M. Gambuzza, C. Beninati, and G. Teti. 1997. Role of interleukin 12 in experimental neonatal sepsis caused by group B streptococci. Infect. Immun. 65: 3731–3735. 9284145 PMC175532
  32. [34]Kovarik, J., X. Martinez, M. Pihlgren, P. Bozzotti, M.H. Tao, T.J. Kipps, T.F. Wild, P.H. Lambert, and C.A. Siegrist. 2000. Limitations of in vivo IL-12 supplementation strategies to induce Th1 early life responses to model viral and bacterial vaccine antigens. Virology. 268: 122–131. 10683334
  33. [35]Peng, S.L. 2005. Signaling in B cells via Toll-like receptors. Curr. Opin. Immunol. 17: 230–236. 15886111
  34. [36]Pasare, C., and R. Medzhitov. 2005. Control of B-cell responses by Toll-like receptors. Nature. 438: 364–368. 16292312
  35. [37]Hardy, R.R., and K. Hayakawa. 2001. B cell development pathways. Annu. Rev. Immunol. 19: 595–621. 11244048
  36. [38]Bhat, N.M., A.B. Kantor, M.M. Bieber, A.M. Stall, L.A. Herzenberg, and N.N. Teng. 1992. The ontogeny and functional characteristics of human B-1 (CD5+ B) cells. Int. Immunol. 4: 243–252. 1377947
  37. [39]Theofilopoulos, A.N., R. Baccala, B. Beutler, and D.H. Kono. 2005. Type I interferons (alpha/beta) in immunity and autoimmunity. Annu. Rev. Immunol. 23: 307–336. 15771573
  38. [41]Ito, S., P. Ansari, M. Sakatsume, H. Dickensheets, N. Vazquez, R.P. Donnelly, A.C. Larner, and D.S. Finbloom. 1999. Interleukin-10 inhibits expression of both interferon alpha- and interferon gamma- induced genes by suppressing tyrosine phosphorylation of STAT1. Blood. 93: 1456–1463. 10029571
  39. [42]Karaghiosoff, M., R. Steinborn, P. Kovarik, G. Kriegshauser, M. Baccarini, B. Donabauer, U. Reichart, T. Kolbe, C. Bogdan, T. Leanderson, et al. 2003. Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock. Nat. Immunol. 4: 471–477. 12679810
  40. [43]Tassiulas, I., X. Hu, H. Ho, Y. Kashyap, P. Paik, Y. Hu, C.A. Lowell, and L.B. Ivashkiv. 2004. Amplification of IFN-alpha-induced STAT1 activation and inflammatory function by Syk and ITAM-containing adaptors. Nat. Immunol. 5: 1181–1189. 15467722
  41. [44]Gautier, G., M. Humbert, F. Deauvieau, M. Scuiller, J. Hiscott, E.E. Bates, G. Trinchieri, C. Caux, and P. Garrone. 2005. A type I interferon autocrine–paracrine loop is involved in Toll-like receptor–induced interleukin-12p70 secretion by dendritic cells. J. Exp. Med. 201: 1435–1446. 15851485 PMC2213193
  42. [45]Pollara, G., M.E. Handley, A. Kwan, B.M. Chain, and D.R. Katz. 2006. Autocrine type I interferon amplifies dendritic cell responses to lipopolysaccharide via the nuclear factor-kappaB/p38 pathways. Scand. J. Immunol. 63: 151–154. 16499567
  43. [46]Katakura, K., J. Lee, D. Rachmilewitz, G. Li, L. Eckmann, and E. Raz. 2005. Toll-like receptor 9-induced type I IFN protects mice from experimental colitis. J. Clin. Invest. 115: 695–702. 15765149 PMC1051992
  44. [47]Ho, H.H., and L.B. Ivashkiv. 2006. Role of STAT3 in type I interferon responses. Negative regulation of STAT1-dependent inflammatory gene activation. J. Biol. Chem. 281: 14111–14118. 16571725
  45. [48]Dalod, M., T.P. Salazar-Mather, L. Malmgaard, C. Lewis, C. Asselin-Paturel, F. Briere, G. Trinchieri, and C.A. Biron. 2002. Interferon α/β and interleukin 12 responses to viral infections: pathways regulating dendritic cell cytokine expression in vivo. J. Exp. Med. 195: 517–528. 11854364 PMC2193614
  46. [49]Krug, A., A.R. French, W. Barchet, J.A. Fischer, A. Dzionek, J.T. Pingel, M.M. Orihuela, S. Akira, W.M. Yokoyama, and M. Colonna. 2004. TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity. 21: 107–119. 15345224
  47. [50]Fujii, S., K. Shimizu, T. Shimizu, and M.T. Lotze. 2001. Interleukin-10 promotes the maintenance of antitumor CD8(+) T-cell effector function in situ. Blood. 98: 2143–2151. 11568001
  48. [51]Fillatreau, S., C.H. Sweenie, M.J. McGeachy, D. Gray, and S.M. Anderton. 2002. B cells regulate autoimmunity by provision of IL-10. Nat. Immunol. 3: 944–950. 12244307
  49. [52]Turner, M., P.J. Mee, A.E. Walters, M.E. Quinn, A.L. Mellor, R. Zamoyska, and V.L. Tybulewicz. 1997. A requirement for the Rho-family GTP exchange factor Vav in positive and negative selection of thymocytes. Immunity. 7: 451–460. 9354466
  50. [53]Gilliet, M., A. Boonstra, C. Paturel, S. Antonenko, X.L. Xu, G. Trinchieri, A. O'Garra, and Y.J. Liu. 2002. The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 195: 953–958. 11927638 PMC2193725
  51. [54]Inaba, K., M. Inaba, N. Romani, H. Aya, M. Deguchi, S. Ikehara, S. Muramatsu, and R.M. Steinman. 1992. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 176: 1693–1702. 1460426 PMC2119469

Cited by

Sorted by citations

Authors
Zhang, X., Deriaud, E., Jiao, X., Braun, D., Leclerc, C., & Lo-Man, R.
Affiliations
  • Inserm (FR)
  • 1Unité Régulation Immunitaire et Vaccinologie
  • Yangzhou University (CN)
  • 4Immunobiologie des Cellules dendritiques, Institut Pasteur, 75724 Paris, Cedex 15, France
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2007-05-07
Volume
204
Issue
5
Pages
1107-1118
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20062013
PMC
PMC2118587
OpenAlex
W2157480948
Cited by
150
References
3
Citations by year
2026: 4 · 2025: 5 · 2024: 8 · 2023: 2 · 2022: 4 · 2021: 8 · 2020: 11 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 7 · 2015: 5 · 2014: 8 · 2013: 9 · 2012: 8
FWCI
5.83
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
type I interferon, neonatal B cells, IL-10, acute inflammation, TLR9, plasmacytoid dendritic cells, myeloid dendritic cells, CD5+ B cells, anti-inflammatory regulation, neonatal immunity, viral and bacterial infections
MeSH terms
Animals, Animals, Newborn, B-Lymphocytes, Dendritic Cells, Flow Cytometry, Inflammation, Interferon Type I, Mice, Inbred C57BL, Interleukin-10, Mice, Knockout, Adoptive Transfer, Toll-Like Receptor 9, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review