MCCIR AZ/GSK Update Seminar
|Dates:||9 May 2016|
|Times:||15:30 - 16:30|
|What is it:||Seminar|
|Organiser:||Manchester Collaborative Centre for Inflammation Research|
|Speaker:||John Grainger , Katie Walwyn-Brown|
A novel population of monocyte-independent gut macrophages are enriched in the lamina propria
Contrasting other barrier sites, where resident macrophages derive from embryonic precursors, resident macrophages in the gut are constantly replenished from blood monocytes. This unique feature of the gut is thought to be dependent on its high commensal burden. These assumptions are based on examination of the total macrophage pool but whether specialised gut macrophage populations with alternative maintenance mechanisms exist is unknown. Here we identify a novel subset of macrophages that are maintained independently of blood monocytes and are highly represented in the lamina propria (LP). These macrophages were enriched for features associated with apoptotic cell uptake suggesting a role in tissue remodelling. Surprisingly, in germ-free animals this monocyte-independent LP macrophage population was unaltered despite the absence of commensal flora. These data challenge the current paradigm of macrophage replenishment in the gut and suggest specific niches are present in the tissue where macrophages are maintained independently of microbiome-driven monocyte recruitment.
Do interactions between Natural Killer cells and Dendritic cells influence inflammation?
Dendritic cells (DCs) play an important role in initiating and influencing immune responses. This is best understood in how DCs switch on T helper cells. DCs exposed to different inflammatory stimuli have been shown to polarise Th1, Th2 and Th17 responses. Cross- talk between Dendritic cells (DCs) and Natural Killer cells (NK cells) is less well understood. Here, we set out to determine how bacterial (LPS) or helminth derived (schistosome egg antigen, SEA) stimuli impact on communication between DCs and NK cells. Human monocyte derived dendritic cells stimulated for 24 hours with LPS or SEA were co-cultured with primary NK cells from the same donor. Then flow cytometry was used to examine expression of DC maturation markers HLA-DR and CD86. As shown previously, co-culture of immature DCs with NK cells leads to upregulation of these markers. In contrast, DCs exposed to SEA do not upregulate maturation markers, suggesting that these DCs are less responsive to maturation by NK cells. There is an increase in cell death of immature DCs co cultured with NK cells compared to LPS treated DCs, supporting previous claims that NK cells edit the DC repertoire to remove immature DCs. Interestingly, SEA matured DCs also have reduced survival when co-cultured with NK cells. Consistent with this, NK cells show increased degranulation during co culture with immature and SEA matured DCs, but not LPS matured DCs. These data imply that NK cells kill immature and helminth-exposed DCs more efficiently than bacterially stimulated DCs. Thus, NK cells may influence the immune response by differentially editing bacterial and helminth stimulated DCs.
Travel and Contact Information
Michael Smith Lecture theatre
Michael Smith Building