Overcoming dendritic cell tardiness to triumph over IL-13 receptor: a strategy for the development of effective pediatric vaccines.
Neonatal exposure to antigen gives rise to a primary response comprising both T helper 1 (Th1) and T helper 2 (Th2) lymphocytes. However, re-encounter with the same antigen yields an indubitably biased response with minimal Th1 but excessive Th2 cells. Since Th1 cells combat microbes while Th2 cells react to allergens, the neonate faces susceptibility to both microbial infections and allergic reactions. The Th1/Th2 imbalance of neonatal immunity stems from a delayed maturation of dendritic cells that yields limited IL-12 cytokine during the neonatal stage. Th1 cells developing under these circumstances up-regulate the IL-13Ralpha1 chain that physically associates with the IL-4Ralpha chain, forming a potentially hazardous heteroreceptor. During re-challenge with antigen, IL-4 from Th2 cells utilizes the heteroreceptor to signal the death of Th1 cells, leading to the Th2 bias of neonatal immunity. Our view to overcome Th1 deficiency is to supplement neonatal immunizations with toll-like receptor ligands that could stimulate maturation of dendritic cells and augment IL-12 production to counter IL-13Ralpha1 up-regulation. This regimen would yield Th1 cells devoid of the heteroreceptor and resistant to IL-4-induced apoptosis. Accordingly, the neonate would have balanced Th1/Th2 immunity and withstand both microbes and allergens. Such approaches could open new avenues for better pediatric vaccines and allergy therapies.
Hoeman
Christine
C
Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Dhakal
Mermagya
M
Zaghouani
Habib
H
D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053660:Receptors, Interleukin-13 / Q000276:immunology*; D014612:Vaccines / Q000276:immunology*
D053660:Receptors, Interleukin-13; D014612:Vaccines