Role of Human Macrophage Polarization in Inflammation during Infectious Diseases

Abstract

Experimental models have often been at the origin of immunological paradigms such as the M1/M2 dichotomy following macrophage polarization. However, this clear dichotomy in animal models is not as obvious in humans, and the separating line between M1-like and M2-like macrophages is rather represented by a continuum, where boundaries are still unclear. Indeed, human infectious diseases, are characterized by either a back and forth or often a mixed profile between the pro-inflammatory microenvironment (dominated by interleukin (IL)-1β, IL-6, IL-12, IL-23 and Tumor Necrosis Factor (TNF)-α cytokines) and tissue injury driven by classically activated macrophages (M1-like) and wound healing driven by alternatively activated macrophages (M2-like) in an anti-inflammatory environment (dominated by IL-10, Transforming growth factor (TGF)-β, chemokine ligand (CCL)1, CCL2, CCL17, CCL18, and CCL22). This review brews the complexity of the situation during infectious diseases by stressing on this continuum between M1-like and M2-like extremes. We first discuss the basic biology of macrophage polarization, function, and role in the inflammatory process and its resolution. Secondly, we discuss the relevance of the macrophage polarization continuum during infectious and neglected diseases, and the possibility to interfere with such activation states as a promising therapeutic strategy in the treatment of such diseases.

M2b macrophage polarization and its roles in diseases

“…Interestingly, CCL1 released from M2b cells is essentially required for maintaining the properties of M2b monocytes/macrophages . Growing evidences have shown that CCL1 is the specific molecular identifier of M2b and may serve as a marker for identifying M2b from the other subtypes of macrophages …”

“…Under normal physiologic conditions, monocytes in the blood retain a quiescent state (M0: CCL1 − , CD163 − , CD14 + ) . During infection, monocytes/macrophages acquire the M1 phenotype (IL‐10 − , IL‐12 + , iNOS + , CXCL9 + ), which is a major effector cells for the first line of host antibacterial defense . Mild burn injury (5% of the total body surface area [TBSA] burn) induces M1 macrophage polarization .…”

“…Additionally, parasitic infections can increase the number and proportion of M2b macrophages (CCL1 + , IL‐10 + , TNF‐α + , IL‐1β + , IL‐6 + , TGF‐β + , CCL17 + ) in the peritoneal cavity, and M2b polarization (IL‐12 low , IL‐10 high , LIGHT + , TNF‐α + ) promotes the persistence of infection . Despite a strong phagocytic capacity, M2b macrophages are not the main cells responsible for killing bacteria . Moreover, M2b monocytes/macrophages not only have no antibacterial effect, but also they increase susceptibility to opportunistic pathogens such as S. aureus , methicillin‐resistant S. aureus (MRSA) (M2b: CCL1 + , CD163 + , CD64 − , CD209 − ), E. faecalis , C. albicans (M2b: IL‐10 + , TNF‐α + , MR + , Dectin‐1 + ), and K. pneumonia .…”

“…M2d macrophages, representing a novel M2 subset that are also known as tumor‐associated macrophages (TAMs), are induced by costimulation with TLR ligands and A2 adenosine receptor (A2R) agonists or by IL‐6 . These cells are mainly characterized by high IL‐10, TGF‐β, and vascular endothelial growth factor (VEGF), and low IL‐12, TNF‐α, and IL‐1β production . They constitute the major inflammatory component in neoplastic tissue, contributing to angiogenesis and cancer metastasis …”

“…These cells are mainly characterized by high IL‐10, TGF‐β, and vascular endothelial growth factor (VEGF), and low IL‐12, TNF‐α, and IL‐1β production . They constitute the major inflammatory component in neoplastic tissue, contributing to angiogenesis and cancer metastasis …”