Activation of Innate Immunity in Graft-versus-Host Disease: Implications for Novel Targets?

Acute graft-versus-host disease (GvHD) is mediated by alloreactive donor-derived T cells with a suitable T cell receptor recognizing recipient major histocompatibility complex or minor histocompatibility antigens. However, the process of T cell activation and tissue injury sensing is also dependent on innate immune cells and non-hematopoietic cells. Different cell types of the innate immune system have the ability to sense danger-associated and pathogen-associated molecular patterns via pattern recognition receptors which can be transmembrane Toll-like receptors or cytoplasmic nucleotide-binding oligomerization domain-like receptors. Infectious stimuli include bacterial, viral, and fungal components, while non-infectious stimuli can be components derived from damaged cells or extracellular matrix. A better understanding of the complex sensing and effector mechanisms of innate immune cells in GvHD may help to improve preventive and therapeutic strategies in GvHD.