Macrophages are innate immune cells whose job is to fight infections. Since we can be exposed to many different types of infections, different flavors (named phenotypes) of macrophages exist. For example, nitric oxide and reactive oxygen species produced by M1 macrophages can kill intracellular viruses and bacteria. In contrast, M2 macrophages help fight extracellular helminth infections and promote wound healing.
However, excessive M1 or M2 responses can also be pathogenic. For example, excessive M1 macrophage responses are involved in tissue damage in autoimmune (such as Multiple Sclerosis, diabetes,…) and inflammatory/injury (spinal cord injury) disease. Similarly, excessive M2 responses are thought to be behind allergic diseases, including asthma.
We are studying molecular mechanisms behind macrophage phenotype and identifying better markers and assays to follow macrophage phenotype. Our work identifying novel markers to distinguish M1 and M2 macrophages was just published in Plos One and we are excited to share it with the macrophage community. This work was born out of the difficulty of evaluating macrophage phenotype. So you know where I’m coming from, please let me explain. I have worked with T cells before and I expected M1 and M2 macrophages to be as easily distinguishable as CD4 and CD8 T cells. We were in for a surprise. Canonical M1 markers, such as iNOS, IL-1, TNF-a, and canonical M2 markers, such as Arginase-1 and CD206, markers are indeed expressed at the RNA level in M1 or M2 macrophages. However, issues with selectivity (Arginase-1 was also expressed in M1 macrophages), protein expression (CD206 and Arginase-1 protein are expressed at low level) or detection (complexity of intracellular flow cytometry) made them less than ideal. Therefore, we undertook the task of identifying novel improved discriminating/selective M1 and M2 markers by a astringent selection process that focused on markers that have opposite expression behavior during differentiation from M0 towards M1 or M2 macrophage. We have identified and validated several markers and share a new flow cytometry assay that can distinguish M1 and M2 macrophages from a mixed population and detect inflammatory macrophages in vivo. Please check out M1/M2 markers paper here.
Nature Immunology Review on macrophages (Jan 2016)
M1/M2 markers manuscript (Dec 2015)