title: Neonatal macrophages express elevated levels of interleukin-27 that oppose immune responses.
abstract: Microbial infections are a major cause of infant mortality worldwide because of impaired immune defences in this population. The nature of this work was to further understand the mechanistic limitations of the neonatal and infant immune response. Interleukin-27 (IL-27) is a heterodimeric cytokine of the IL-12 family that is produced primarily by antigen-presenting cells and is immunosuppressive toward a variety of immune cell types. We show that IL-27 gene expression is elevated in cord blood-derived macrophages relative to macrophages originating from healthy adults. We also evaluated the duration over which elevated IL-27 gene expression may impact immune responses in mice. Age-dependent analysis of IL-27 gene expression indicated that levels of IL-27 remained significantly elevated throughout infancy and then declined in adult mice. Flow cytometric analysis of intracellular cytokine-stained splenocytes further confirmed these results. Interleukin-27 may be induced during pregnancy to contribute to the immunosuppressive environment at the fetal-maternal interface because we demonstrate dose-responsive gene expression to progesterone in macrophages. Neutralization of IL-27 in neonatal macrophages improved the ability of these cells to limit bacterial replication. Moreover, neutralization of IL-27 during incubation with the Mycobacterium bovis bacillus Calmette-Guérin vaccine augmented the level of interferon-γ elicited from allogeneic CD4+ T lymphocytes. This suggests that blocking IL-27 during vaccination and infection may improve immune responses in newborn and infant populations. Furthermore, mice will be a suitable model system to further address these possibilities.
authors: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
authors: Jennifer D
authors: JD
authors: Kraft
authors: Joseph
authors: J
authors: Horzempa
authors: Celestia
authors: C
authors: Davis
authors: Joo-Yong
authors: JY
authors: Jung
authors: Maria Marjorette O
authors: MM
authors: Peña
authors: Cory M
authors: CM
authors: Robinson
mesh_terms: D000367:Age Factors; D000375:Aging / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D001500:BCG Vaccine / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D011374:Progesterone / Q000494:pharmacology; D013154:Spleen / Q000276:immunology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D001500:BCG Vaccine; C573415:IFNG protein, human; C486767:Il27 protein, mouse; D007378:Interleukins; C464565:MYDGF protein, human; D011374:Progesterone; D007371:Interferon-gamma
keywords: T cells; interferon-γ; interleukin-27; macrophages; neonate