Macrophages, immune cells of the innate immune system, are important throughout pregnancy. They are well known for their role as antigen presenting cells. But depending on the signals macrophages receive from their environment, they are able to adapt various other functions (e.g. induce tissue repair or regulate immune responses) and even change functions if necessary¹.

To exert these different functions, macrophages exist in a spectrum of subtypes. In principle, you can distinguish three types of macrophages: M1 macrophages (classically activated), M2 macrophages (alternatively activated) and, M2-like macrophages/M2c (regulatory macrophage)^*. M1 macrophages are typically involved in inflammation and tissue damage and are characterized by the expression of MHCII and cytokines like IFNγ and TNFα. M2 macrophages exert immunosuppressive actions and are characterized by the expression of CD206 and arginase-1. M2-like macrophages are involved in tissue repair mechanisms but also highly associated with fibrosis. M2 and M2-like macrophages share many markers. Currently, IL-10 is the only reliable marker known to distinguish between M2 and M2-like macrophages².

At the maternal-fetal interface, decidual macrophages are, together with NK cells, the most prominent immune cells during early pregnancy³. They do not belong to either of the above mentioned subtypes, but seem to express a characteristic phenotype. The decidual macrophage phenotype resembles the M2-like macrophages^4-6 (see below in the table), but does exert a different expression profile: CD209⁺, CD163^high, CD206⁺ (mannose receptor), CD304⁺ (NRP-1), ICAM-3⁺, CD11c^low. They induce maternal-fetal tolerance and placental development by expressing high phagocytic activity, stimulating angiogenesis and, inducing vascular remodeling³. The balance between M1/M2 macrophages is often used as a measure for pregnancy outcome or pregnancy related disorders^{5, 7}, for example miscarriages⁸.

Monocytes are important precursor cells of tissue macrophages. They circulate in the bloodstream, ready to act upon danger signals and penetrate damaged tissues. Three monocyte subpopulations can be distinguished based on their expression pattern of CD14 and CD16; classical monocyte CD14^highCD16^neg, non-classical monocyte (CD14^dimCD16^pos) and the intermediate monocyte (CD14^highCD16^pos). In pregnancy, changes in monocyte subsets are associated with pre-eclampsia and intrauterine fetal growth restriction^{9, 10}.

The most important markers, cytokines and stimulants to identify and stimulate macrophages are listed below. Are you interested in other markers, different fluorochromes or need help creating a panel for your research purpose? Contact us at techsupport@iqproducts.nl.

*Macrophage nomenclature has been debated for years¹¹. Here we mention the most common names for each subtype

References

• Gordon S., et al. Monocyte and macrophage heterogeneity. Nature Rev. Immunol, 5:953-964, (2005).

• Mosser D.M., et al. Exploring the full spectrum of macrophage activation. Nature Rev. Immunol, 8:958-969, (2008).

• Faas M.M., et al. Uterine NK cells and macrophages in pregnancy. Placenta, 56:44-52, (2017)

• Erlebacher A. Immunology of the maternal-fetal interface. Ann. Rev. Immunol. 31:387-411, (2013)

• Zhang Y.H., et al. Modulators of the balance between M1 and M2 macrophages during pregnancy. Front. Immunol. 8:120, (2017)

• Svensson J., et al. Macrophages at the fetal-maternal interface express markers of alternative activation and are induced by M-CSF and IL-10. J. Immunol. 187:3671-3682, (2011)

• Brown M.B., et al. M1/M2 macrophages polarity in normal and complicated pregnancy. Front. Immunol. 5:606, (2014)

• Shimada S., et al. Decidual CD68⁺HLA-DR⁺CD163^– M1 macrophages increase in miscarriages with normal fetal chromosome. Am. J. Reprod. Immunol. 79:e12791, (2018)

• Faas M.M., et al. Monocytes and macrophages in pregnancy and pre-eclampsia. Front. Immunol. 5:298, (2014)

• Alahakoon T.I., et al. Distribution of monocyte subsets and polarization in preeclampsia and intrauterine fetal growth restriction. J. Obstet. Gynaecol. Res. 29, (2018)

• Murray P.J., et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 41(1):14-20, (2014)