Macrophage polarisation: the impact of M1 versus M2 polarisation on host innate immune responses to bacterial infection
Foley, Niamh M.
University College Cork
Background and Aim: Infection is a global burden causing millions of deaths per annum worldwide. In the US sepsis is the tenth leading cause of death with the mortality associated with severe sepsis estimated at 30-50%. Innate immunity is a generic response mediated by the host to protect it from bacterial infection. The recognition of foreign microbes leads to activation of pattern recognition receptors and recruitment of macrophages. In acute bacterial infections, activated macrophages polarised to M1 or M2 states play a major role in the host cytokine response which drives the immune response until the host has overcome the invading microbial pathogen. The aim of this study was to 1) to characterise the cytokine profile of M1 and M2 polarised macrophages 2) to investigate the changes in the cytokine profile of polarised macrophages in response to bacterial stimulation 3) to examine the role of the MAPK and NFκB signalling pathways in the response of naïve and polarised macrophages to bacterial infection. Results: (i) polarisation of macrophages to an M1 state resulted in a higher secretion of pro-inflammatory cytokines (IL-6, IL12p70 and TNF-.). (ii) following bacterial stimulation M1 polarised macrophages had reduced pro-inflammatory cytokine release. (iii) M1 polarised macrophages have reduced MAPK and NFκB signalling as detected by western blot analysis. Conclusion: Following bacterial stimulation M1 polarised macrophages had reduced pro-inflammatory cytokine release which may in part be due to reduced MAPK and NFκB signalling. This data suggests that M1 polarisation states may play important roles in an endotoxin tolerant phenomenon in acute bacterial sepsis.
Macrophage polarisation , Sepsis
Foley, N. M. 2015. Macrophage polarisation: the impact of M1 versus M2 polarisation on host innate immune responses to bacterial infection. MD Thesis, University College Cork.