Experimental models have often been at the origin of immunological paradigms such as the m1m2 dichotomy following macrophage polarization. Trpm7 regulates proliferation and polarisation of macrophages. Pdf macrophages populate virtually all tissues in the body and have a myriad of functions in host defense and. Such reprogramming allowed nongrowing salmonella cells to survive for extended periods in their. Macrophage diversity and polarization in atherosclerosis. Macrophage polarization state depends on their microenvironment that provides the cues for reversible states of activation. Gordon and martinez, 2010, lawrence and natoli, 2011, mantovani et al. As expected, nox2 expression was the highest in both macrophage populations, followed by nox4 and nox1 supplemental figure 3. M1 and m2 macrophage polarization in vitro with exposure. This changeability is often called polarization or activation.
A first network tipping the balance in macrophage activation is represented by transcription factors, with signaltransducer and activator of transcription protein. The subtypes of the m2 phenotype are firstly defined in the macrophage activation. The plastic gene expression profile of macrophages is influenced by the type of stimulating. Macrophages are the major producers of cytokines in inflammation, and the factors they produce depend upon their activation state or polarization. Review article full text access control of macrophage metabolism and activation by mtor and akt signaling. The balance between activation of stat1 and stat3stat6 finely regulates macrophage polarization and activity. Card9 is required for classical macrophage activation and the induction of protective immunity against pulmonary cryptococcosis althea campuzano, anatalia castrolopez, amanda j. A m1 and m2 macrophage polarization model was established using the human monocytic cell line thp1. Persisters reprogram macrophages by means of effectors secreted by the salmonella pathogenicity island 2 type 3 secretion system.
Transcriptional regulation of macrophages polarization by. Macrophages exposed to the m1 or classic activation express cytokine receptors whereas m2a or alternative activated macrophages are characterized by abundant levels of nonopsonic receptors e. Macrophage activation and polarization 455 figure 2. The type, timing, and concentration of these stimuli determine the range of immune responses. Like the biblical tower of babel, macrophage activation encompasses a panoply of descriptors used in different ways. Role of human macrophage polarization in inflammation. Peroxisome proliferatoractivated receptors are a group of transcriptional factors belonging to the ligandactivated nuclear hormone receptor superfamily, including ppar.
Ab description of macrophage activation is currently contentious and confusing. A current hypothesis suggests that macrophage activation in osteolysis may be polarized. Interestingly, the mir155 levels in macrophages were strikingly decreased following macrophage m1tom2 re polarization figure 1c but elevated during macrophage m2tom1 re polarization figure 1d. Molecular mechanisms of macrophage polarization in cerebral. B activation by p50 homodimers has been associated with m2 differentiation. In recent years, it has become apparent that macrophages are also. We summarize the roles of m1m2 polarization in host defense and the mechanisms. Editor in chief, encyclopedia of immunobiology, vol. The activation of microglia to an m1 phenotype appears mainly in the acute phase after sah and m2 microglial activation occurs in the subacute and delayed phase.
Macrophages can have beneficial as well as detrimental effects for the outcome of several diseases depending on. This is a pdf file of an unedited manuscript that has. Moreover, inflammatory signals of microbial or leukocyte origin drive different forms of macrophage activation. Activation of macrophages has emerged as a key area of immunology, tissue homeostasis, disease pathogenesis, and resolving and nonresolving inflammation biswas and mantovani, 2010, gordon and martinez, 2010, lawrence and natoli, 2011, mantovani et al. Macrophage polarization is associated with distinctive gene signatures. As a result of exposure to different tissue environments, macrophage polarization is likely to span a continuum of functional states. Macrophage polarization is a process by which macrophages adopt different functional programs in response to the signals from their microenvironment. Alternatively, activated m2 microglia are categorized into four subtypes, m2a, m2b, m2c, and m2d. Macrophage activation and polarization in postinfarction. We will also discuss potential targets for ca therapies. Infection of c3h mice with borrelia burgdorferi, the causative agent of lyme disease, reliably produces an infectious arthritis and carditis that peak around 3 weeks postinfection and then spontaneously resolve. Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Card9 is required for classical macrophage activation and.
For polarization to an m1 phenotype the cells are treated for 16 hr with 50 ngml of escherichia coli lps sigma and uml of recombinant ifn. This ability is connected to their multiple roles in the organism. Macrophages represent one of the most numerous and diverse leukocyte types in the body. Martinez and antonio sica and alberto mantovani and massimo locati, journalfrontiers in bioscience.
The lack of consensus on how to define macrophage activation in experiments. Macrophage activation and polarization request pdf. Expanding on previous studies of m1 and m2 markers, they found that while m1 polarization was associated with dramatic changes in the transcriptome, m2 polarization resulted in minimal alterations in gene expression. Repolarization of tumorassociated macrophages to pro. Microglial activation and polarization after subarachnoid. Macrophages play important roles in health and disease. Olszewski,b,c anutosh ganguly,c,d chrissy leopold wager, achiungyu hung, floyd l. Gordon s, martinez fo 2010 alternative activation of macrophages. Human perifollicular macrophages undergo apoptosis. Salmonella persisters undermine host immune defenses.
Macrophage polarization during murine lyme borreliosis. Different stages of monocyte macrophage vital activity are actively suggested as targets to modulate its activation and polarization. The description of macrophage activation status is contentious and confusing. The jmjd3irf4 axis regulates m2 macrophage polarization and host responses against helminth infection. Macrophages are activated by various signals to acquire specialized functions 1, 2. Pivotal regulators of tissue homeostasis and cancer. Macrophage activation and polarization sciencedirect. Lagoudakid, eleftheria ieronymaki a, ariadne androulidaki, maria venihaki, andrew n. The crosstalk between the m1m2 macrophage polarizing pathways is also indicated. Cells of the innate immune system j macrophage activation and polarization 291 authors personal copy variables i. Macrophage polarization model from thp1 monocytic cells. Pdf macrophage activation and polarization researchgate.
Macrophages are widely distributed immune system cells that play an indispensable role in homeostasis and defense. One of the sides is blocking the attraction of inflammatory monocytes. Macrophage biology, classification, and phenotype in. Ivashkiv,9 toby lawrence,10 massimo locati,11 alberto mantovani,11 fernando o. To investigate human macrophage function, wnt secretion and the polarization of perifollicular macrophages were investigated using quantitative immunohistomorphometry through the hair cycle.
The results suggest that mir155 may play a critical role in promoting macrophage polarization to the m1 phenotype. Ppars have been shown to transcriptionally regulate the activation. Their functions range from sensing pathogens to digesting cell debris, modulating inflammation, and producing key cytokines and other regulatory factors throughout the body. Macrophage activation and polarization modify p2x7 receptor. Based on immunological responses, the macrophages are classified into activated macrophage m1 macrophages participating in the responses of type i helper t th1 cells to pathogens and alternatively activated macrophages m2 macrophages in response to interleukin il. Krausgruber t, blazek k, smallie t, alzabin s, lockstone h, sahgal n.
Description of macrophage activation is currently contentious and confusing. The chemokine system in diverse forms of macrophage activation and polarization. Macrophage polarization has been suggested to drive inflammation, the clearance of bacteria, and tissue repair and resolution in a variety of infectious disease models. Immunity perspective macrophage activation and polarization. These effectors dampened proinflammatory innate immune responses and induced antiinflammatory macrophage polarization.
Their functions include immune surveillance, bacterial killing, tissue remodelling and repair, clearance of cell debris and more gordon and taylor, 2005. The treated macrophages were harvested in 3 ml of pbs, lysed using 100. Role of microrna in macrophage activation and polarization. Diversity and plasticity are hallmarks of the monocyte macrophage system. The major pathways of macrophage polarization are outlined. Therapies targeting macrophage activation or preventing the m1m2 imbalance may potentially halt aneurysm formation and rupture. The m1 microglial polarization is characterized by an increase in the expression of proinflammatory molecules. Perspective macrophage activation and polarization.
However, this clear dichotomy in animal models is not as obvious in humans, and the separating line between m1like and m2like macrophages is rather represented by a continuum, where boundaries are still unclear. During microbial infection, macrophages are activated by pathogenassociated molecular patterns such as lps to an inflammatory phenotype that is characterized by production of inflammatory cytokines and induction of antimicrobial activities. Role of tumorassociated macrophages in tumor progression and invasion. The contribution of inflammation to bone loss is well documented in arthritis and other diseases with an emphasis on how inflammatory cytokines promote osteoclastogenesis. Furthermore, they are important regulators and promoters of many cardiovascular disease programs. The decreased m1 polarization and elevated m2 phenotype are observed with the remarkable downregulation of tnf. M1 macrophages may promote an inflammatory response early with production of mediators such as il1, il6, il8, mmps, and. In order to analyze if nox4 influences macrophage polarization, we isolated. Irf5 promotes inflammatory macrophage polarization and th1th17 responses.
Akt1 and akt2 protein kinases differentially contribute to. Vegf may contribute to macrophage recruitment and m2. Ronny milde, matthieu pesant, massimo locati, fernando o. Macrophages are an essential component of innate immunity and play a vital role in inflammation and host defense. Transcriptional profiling of the human monocyteto macrophage differentiation and polarization. Human and murine macrophages were generated and analyzed for the expression of individual nadph oxidases. Macrophages undergo activation in response to a broad spectrum of environmental signals. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and the normal tissue environment. In contrast, m2 macrophage activation is induced by fungal cells, immune.