DEC 02, 2014
By Michael E. Zegans, MD
Uveitis
This study’s authors report that innate immunity can be "trained" to offer nonspecific protection against a secondary pathogen challenge, research which marks an important step forward in understanding the molecular biology of trained innate immune response.
Trained immunity refers to the memory characteristics of the innate immune system. Memory traits of innate immunity have been reported in plants and invertebrates, as well as in mice lacking functional T and B cells that are protected against secondary infections after exposure to certain infections or vaccinations.
This phenomenon is of particular interest to ophthalmologists since these responses maintain the ocular surface as a mucosal niche with almost uniquely low levels of microbial colonization.
A more detailed understanding of the regulation of these innate immune responses is critical to learning how to manipulate these responses to the benefit of our patients. In some instances, induction of trained immunity could be a targeted therapeutic goal, while in others, such as in cases of chronic inflammation, inhibiting these mechanisms could provide significant improvement in therapeutic outcomes.
The authors studied a model of trained immunity in mice in which β-glucan, a cell wall polysaccharide component from fungi, induces nonspecific protection against infections. By studying genome-wide transcriptome and histone modification profiles they found that elevated glycolysis is the metabolic basis for trained immunity, providing the energy and metabolic substrates for the increased activation of trained immune cells.
They identified specific metabolic pathways and found that trained immunity was completely abrogated in monocytes from dectin-1-deficient mice. Blocking of the mTOR-HIF-1α pathway by chemical inhibitors inhibited trained immunity. HIF1α gene knockout mice also lacked the ability to develop a β-glucan-induced protective response to Staphylococcus aureus sepsis.