Viruses and Glucocorticoids ‘Cooperate’ to Induce Interleukin-10 Production: Implications for Stress-Induced Immunosuppression and Exacerbations of Asthma
A study published in the May 2013 issue of PLoS One may indicate a novel, unrecognized interaction between viruses and the glucocorticoid (GC)-signaling system that results in the induction of interleukin (IL)-10 production by dendritic cells (DCs).
In this report, Sinnie Ng and colleagues from the National Institutes of Child Health and Human Development, and the National Cancer Institute, National Institutes of Health (NIH), US, targeted DCs, professional antigen presenting cells that activate T cells and other immune components. Dendritic cells act as sentinels of the immune system, capturing and processing pathogens and presenting their antigens to T cells. Little is known, however, about how GCs regulate the immune response, conducted by DCs, in particular during viral infection.
By using real time PCR and other techniques, the authors found that IL-10 mRNA abundance and IL-10 secretion were strongly upregulated in DCs when they were pretreated with GCs before viral infection. The authors further screened the signaling pathway responsible for this action, and found that extracellular signal-regulated kinase (ERK) inhibitors abolished the cooperation between GCs and viral infection in DCs.
This study indicates that viruses and GCs cooperatively increase IL-10 production by potentiating the transcriptional activity of GC receptors in DCs, through which viruses appear to facilitate their own propagation in infected hosts.
It is known that IL-10, a major anti-inflammatory cytokine, has potent immunosuppressive actions and that upon viral infection, circulating levels of IL-10 increase to facilitate resolution of inflammation promoted by pro-inflammatory cytokines. Of note, Epstein-Barr virus and the varicella-zoster virus, encode IL-10-like molecules, which share immunosuppressive properties of host IL-10, while persistent infection or the reactivation of Mycobacterium tuberculosis infection is also associated with excessive production of IL-10.
Thus, this study may provide some further insights into mechanisms driving stress-induced increased susceptibility to viral infection as documented by previous research. Furthermore, as the link between viral infections, psychological stress and asthma exacerbations is well-known, the study helps explain this connection as increased IL-10 production and resulting activation of T helper (Th)2-driven humoral immunity play important roles in asthma development.
Source: PLoS One, 2013, 8(5):e63587. doi: 10.1371/journal.pone.0063587. Print 2013.
Read More: plosone.org