Stroma: the forgotten cells of innate immune memory

Summary
All organisms are exposed constantly to a variety of infectious and injurious
stimuli. These induce inflammatory responses tailored to the threat posed.
While the innate immune system is the front line of response to each
stimulant, it has been considered traditionally to lack memory, acting in a
generic fashion until the adaptive immune arm can take over. This outmoded
simplification of the roles of innate and acquired arms of the immune system
has been challenged by evidence of myeloid cells altering their response to
subsequent encounters based on earlier exposure. This concept of ‘innate
immune memory’ has been known for nearly a century, and is accepted
among myeloid biologists. In recent years other innate immune cells, such as
natural killer cells, have been shown to display memory, suggesting that
innate immune memory is a trait common to several cell types. During the
last 30 years, evidence has slowly accumulated in favour of not only
haematopoietic cells, but also stromal cells, being imbued with memory
following inflammatory episodes. A recent publication showing this also to be
true in epithelial cells suggests innate immune memory to be widespread, if
under-appreciated, in non-haematopoietic cells. In this review, we will
examine the evidence supporting the existence of innate immune memory in
stromal cells. We will also discuss the ramifications of memory in long-lived
tissue-resident cells. Finally, we will pose questions we feel to be important in
the understanding of these forgotten cells in the field of innate memory.