Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens
| Autor: | Sarah W. Goes, R. L. Chelvarajan, J S Bryson, Subbarao Bondada, J. Van Willigen, I. E. Doubinskaia, Diana Lowery Flanagan, S. M. Collins, W. J. S. De Villiers |
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| Rok vydání: | 2004 |
| Předmět: |
Lipopolysaccharides
Male Lipopolysaccharide CD14 Immunology Lipopolysaccharide Receptors Receptors Cell Surface Biology Mice chemistry.chemical_compound Antigen Escherichia coli Animals Immunology and Allergy Secretion RNA Messenger B-Lymphocytes Mice Inbred BALB C Membrane Glycoproteins Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Macrophages Toll-Like Receptors Interleukin hemic and immune systems Cell Biology Macrophage Activation Interleukin-12 Toll-Like Receptor 2 Interleukin-10 Mice Inbred C57BL Toll-Like Receptor 4 Animals Newborn chemistry biology.protein Female Tumor necrosis factor alpha Cytokine secretion Antibody Haptens Interleukin-1 |
| Zdroj: | Journal of Leukocyte Biology. 75:982-994 |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | Neonates do not respond to thymus-independent (TI) antigens (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 (MΦ). Lipopolysaccharide (LPS) failed to induce neonatal MΦ to produce interleukin (IL)-1β and tumor necrosis factor α (TNF-α) mRNA and to secrete IL-1β, IL-12, and TNF-α. However, LPS induced neonates to secrete some IL-6 and three- to fivefold more IL-10 than adults. Accordingly, adding adult but not neonatal MΦ 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-1β and IL-6 production, as IL-10−/− neonatal MΦ responded to LPS by secreting more IL-1β and IL-6 than wild-type (WT) neonatal MΦ. When cultures were supplemented with a neutralizing Ab to IL-10, WT neonatal MΦ secreted increased amounts of IL-6 and allowed neonatal MΦ 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 MΦ to secrete cytokines, such as IL-1β and IL-6, probably as a result of an excess production of IL-10. This dysregulated cytokine secretion by neonatal MΦ may be a result of a reduction in expression of Toll-like receptor-2 (TLR-2) and TLR-4 and CD14. |
| Databáze: | OpenAIRE |
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