Pathogen manipulation of cIL-10 signaling pathways: opportunities for vaccine development?

Interleukin-10 (IL-10) is a tightly regulated, pleiotropic cytokine that has profound effects on all facets of the immune system, eliciting cell-type-specific responses within cells expressing the IL-10 receptor (IL-10R). It is considered a master immune regulator, and imbalances in IL-10 expression, resulting from either inherent or infectious etiologies, have far reaching clinical ramifications. Regarding infectious diseases, there has been accumulating recognition that many pathogens, particularly those that establish lifelong persistence, share a commonality of their natural histories: manipulation of IL-10-mediated signaling pathways. Multiple viral, bacterial, protozoal, and fungal pathogens appear to have evolved mechanisms to co-opt normal immune functions, including those involving IL-10R-mediated signaling, and immune effector pathways away from immune-mediated protection toward environments of immune evasion, suppression, and tolerance. As a result, pathogens can persist for the life of the infected host, many of whom possess otherwise competent immune systems. Because of pathogenic avoidance of immune clearance, persistent infections can exact incalculable physical and financial costs, and represent some of the most vexing challenges for improvements in human health. Enormous benefits could be gained by the development of efficient prevention and/or therapeutic strategies that block primary infection, or clear the infection. There are now precedents that indicate that modalities focusing on pathogen-mediated manipulation of IL-10 signaling may have clinical benefit.