Neonatal macrophages express elevated levels of interleukin-27 that oppose immune responses.
Kraft JD, et al.
Immunology. 2013 Mar 6.
Microbial infections are a major cause of infant mortality worldwide as a result of impaired immune defenses in this population. The nature of this work was to further understand the mechanistic limitations of the neonatal and infant immune response. Interleukin (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. Here 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 in 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 remain significantly elevated throughout infancy and then declined in adult mice. Flow cytometric analysis of intracellular cytokine-stained splenocytes further confirmed these results. IL-27 may be induced during pregnancy to contribute to the immunosuppressive environment at the fetal-maternal interface since 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 BCG vaccine augmented the level of interferon (IFN)-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
Source: Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina.