HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print February 24, 2004

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0403179v1 75/6/982    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chelvarajan, R. L. Articles by Bondada, S. Search for Related Content PubMed PubMed Citation Articles by Chelvarajan, R. L. Articles by Bondada, S.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0403179

Received for publication April 24, 2003.
Revised December 20, 2003.
Accepted for publication January 22, 2004.

Article

Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens

R. L. Chelvarajan ^*, S. Collins , I. E. Doubinskaia , S. Goes ^*, J. Van Willigen , D. Flanagan ^*, W. J. S. de Villiers , J. S. Bryson , and S. Bondada ^*@

Departments of *Microbiology & Immunology and Internal Medicine and Sanders Brown Center on Aging, University of Kentucky, Lexington

^@ To whom correspondence should be addressed. E-mail: bondada{at}uky.edu.

	Abstract

Neonates do not respond to thymus-independent (TI) antigen (Ag), making them vulnerable to infection with encapsulated bacteria. The antibody (Ab) response of adult and neonatal B cells to TI Ag requires certain cytokines, which are provided by T cells or macrophages (M). Lipopolysaccharide (LPS) failed to induce neonatal M to produce interleukin (IL)-1 and tumor necrosis factor (TNF-) mRNA and to secrete IL-1, IL-12, and TNF-. However, LPS induced neonates to secrete some IL-6 and three- to fivefold more IL-10 than adults. Accordingly, adding adult but not neonatal M could restore the response of purified adult B cells to trinitrophenol (TNP)-LPS, a TI Ag. Increased IL-10 is causally related to decreased IL-1 and IL-6 production, as IL-10^-/- neonatal M responded to LPS by secreting more IL-1 and IL-6 than wild-type (WT) neonatal M. When cultures were supplemented with a neutralizing Ab to IL-10, WT neonatal M secreted increased amounts of IL-6 and allowed neonatal M to promote adult B cells to mount an Ab response against TNP-LPS. Thus, neonates do not respond to TI Ag as a result of the inability of neonatal M to secrete cytokines, such as IL-1 and IL-6, probably as a result of an excess production of IL-10. This dysregulated cytokine secretion by neonatal M may be a result of a reduction in expression of Toll-like receptor-2 (TLR-2) and TLR-4 and CD14.

Key Words: B lymphocytes • cytokines • LPS • suppression

This article has been cited by other articles:

				S. Kanswal, N. Katsenelson, A. Selvapandiyan, R. J. Bram, and M. Akkoyunlu Deficient TACI Expression on B Lymphocytes of Newborn Mice Leads to Defective Ig Secretion in Response to BAFF or APRIL J. Immunol., July 15, 2008; 181(2): 976 - 990. [Abstract] [Full Text] [PDF]

				J. Zhao, K. D. Kim, X. Yang, S. Auh, Y.-X. Fu, and H. Tang From the Cover: Hyper innate responses in neonates lead to increased morbidity and mortality after infection PNAS, May 27, 2008; 105(21): 7528 - 7533. [Abstract] [Full Text] [PDF]

				L. Chelvarajan, D. Popa, Y. Liu, T. V. Getchell, A. J. Stromberg, and S. Bondada Molecular mechanisms underlying anti-inflammatory phenotype of neonatal splenic macrophages J. Leukoc. Biol., August 1, 2007; 82(2): 403 - 416. [Abstract] [Full Text] [PDF]

				W. E. Walker and D. R. Goldstein Neonatal B Cells Suppress Innate Toll-Like Receptor Immune Responses and Modulate Alloimmunity J. Immunol., August 1, 2007; 179(3): 1700 - 1710. [Abstract] [Full Text] [PDF]

				T. Peters, W. Bloch, C. Wickenhauser, S. Tawadros, T. Oreshkova, D. Kess, T. Krieg, W. Muller, and K. Scharffetter-Kochanek Terminal B cell differentiation is skewed by deregulated interleukin-6 secretion in {beta}2 integrin-deficient mice J. Leukoc. Biol., September 1, 2006; 80(3): 599 - 607. [Abstract] [Full Text] [PDF]

				O. Levy, E. E. Suter, R. L. Miller, and M. R. Wessels Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells Blood, August 15, 2006; 108(4): 1284 - 1290. [Abstract] [Full Text] [PDF]

				P. Henneke and R. Berner Interaction of neonatal phagocytes with group B streptococcus: recognition and response. Infect. Immun., June 1, 2006; 74(6): 3085 - 3095. [Full Text] [PDF]

				R. L. Chelvarajan, Y. Liu, D. Popa, M. L. Getchell, T. V. Getchell, A. J. Stromberg, and S. Bondada Molecular basis of age-associated cytokine dysregulation in LPS-stimulated macrophages J. Leukoc. Biol., June 1, 2006; 79(6): 1314 - 1327. [Abstract] [Full Text] [PDF]

				O. Levy Innate immunity of the human newborn: distinct cytokine responses to LPS and other Toll-like receptor agonists Innate Immunity, April 1, 2005; 11(2): 113 - 116. [Abstract] [PDF]

				R. L. Chelvarajan, S. M. Collins, J. M. Van Willigen, and S. Bondada The unresponsiveness of aged mice to polysaccharide antigens is a result of a defect in macrophage function J. Leukoc. Biol., April 1, 2005; 77(4): 503 - 512. [Abstract] [Full Text] [PDF]