UC Berkeley

Most of our understanding about the cellular response to microbes by innate immune cells is shaped by our work with macrophages in culture. Because there exist such a large number of specialized innate immune cells, it stands to reason that the response to pathogen by different cell types will be specialized, even if the same innate immune receptors are used - my work documents two such incidents. Here we report that TLR2 activation by multiple viruses leads to production of type I interferon (IFN) only in Ly6Chigh inflammatory monocytes. Importantly, TLR2-dependent induction of type I IFN only occurs in response to viruses, not bacterial TLR2 ligands, indicating that TLR2 is capable of discriminating between these pathogen classes. Separately, we demonstrate that bone marrow neutrophils need to be "armed" by GM-CSF before they respond to TLR ligands, unlike other innate immune cells. We then go on to show that certain pro-inflammatory signals in vivo are sufficient to "arm" neutrophils so they could more readily respond to pathogen associated microbial patterns.