Pub Date : 2019-10-28DOI: 10.5772/intechopen.88171
M. Wasson, S. Kapoor, M. Garg, Sandhya Singh, H. Prakash
Macrophages are the special cells of the immune system and play both immu-nological and physiological role. One of the peculiar characteristics of macrophages is that they are double-edged and highly plastic component of immune system. Due to this characteristic, they are responsible for both progressions as well control of a variety of inflammatory, infectious and metabolic diseases and cancer. These are found in the body in three major phenotypes, which are known as M0 (also known as naïve); M1 (classically activated macrophages); and/or M2 (alternatively activated macrophages) at normal physiological conditions. We have been exploring macrophages in context of bacterial infection and previ-ously demonstrated that M2 polarization of M1 effector alveolar macrophages during chronic/persistent Chlamydia pneumonia , Mycobacterium tuberculosis and Helicobacter pylori pathogens are decisive for the infection induced cancer development in host. Since chronic infection with these pathogens has been associated with adenocarcinoma, therefore, we feel that disruption of macrophage plasticity plays crucial role in the host for the development of cancer. On the basis of this, we propose that in such pathological conditions, management of M1/M2 imbalance is paramount for minimizing the risk of developing cancer by chronic and persistent infection. macrophage for subverting effector mechanisms during latency. Pathogenic bacteria interfere with various key signaling pathways which are important for the effector responses, e.g., recognition by receptors, uptake, and phagocytosis, lysosomal degradation, and alter signaling pathways and secretion of Th1 cytokines for establishing Th2 bias.
{"title":"Macrophage Polarization Is Decisive for Chronic Bacterial Infection-Induced Carcinogenesis","authors":"M. Wasson, S. Kapoor, M. Garg, Sandhya Singh, H. Prakash","doi":"10.5772/intechopen.88171","DOIUrl":"https://doi.org/10.5772/intechopen.88171","url":null,"abstract":"Macrophages are the special cells of the immune system and play both immu-nological and physiological role. One of the peculiar characteristics of macrophages is that they are double-edged and highly plastic component of immune system. Due to this characteristic, they are responsible for both progressions as well control of a variety of inflammatory, infectious and metabolic diseases and cancer. These are found in the body in three major phenotypes, which are known as M0 (also known as naïve); M1 (classically activated macrophages); and/or M2 (alternatively activated macrophages) at normal physiological conditions. We have been exploring macrophages in context of bacterial infection and previ-ously demonstrated that M2 polarization of M1 effector alveolar macrophages during chronic/persistent Chlamydia pneumonia , Mycobacterium tuberculosis and Helicobacter pylori pathogens are decisive for the infection induced cancer development in host. Since chronic infection with these pathogens has been associated with adenocarcinoma, therefore, we feel that disruption of macrophage plasticity plays crucial role in the host for the development of cancer. On the basis of this, we propose that in such pathological conditions, management of M1/M2 imbalance is paramount for minimizing the risk of developing cancer by chronic and persistent infection. macrophage for subverting effector mechanisms during latency. Pathogenic bacteria interfere with various key signaling pathways which are important for the effector responses, e.g., recognition by receptors, uptake, and phagocytosis, lysosomal degradation, and alter signaling pathways and secretion of Th1 cytokines for establishing Th2 bias.","PeriodicalId":126515,"journal":{"name":"Macrophage Activation - Biology and Disease","volume":"68 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125904185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-09-26DOI: 10.5772/INTECHOPEN.88754
Rhana Berto da Silva Prata, M. G. M. Barbosa, B. Silva, Jéssica Araújo da Paixão de Oliveira, Tamiris Lameira Bittencourt, R. Pinheiro
Leprosy is a chronic infectious disease caused by the intracellular pathogen Mycobacterium leprae . The disease may present different clinical forms depending on the immunological status of the host. M. leprae may infect macrophages and Schwann cells, and recent studies have demonstrated that macrophages are funda-mental cells for determining the outcome of the disease. Skin lesions from patients with the paucibacillary form of the disease present a predominance of macrophages with a pro-inflammatory phenotype (M1), whereas skin lesions of multibacillary patients present a predominance of anti-inflammatory macrophages (M2). More recently, it was shown that autophagy is responsible for the control of bacillary load in paucibacillary macrophages and that the blockade of autophagy is involved in the onset of acute inflammatory reactional episodes in multibacillary cells. So, strategies that aim to induce autophagy in infected macrophages are promising not only to improve the efficacy of multidrug therapy (MDT) but also to avoid the occurrence of reactional episodes that are responsible for the disabilities observed in leprosy patients.
{"title":"Macrophages in the Pathogenesis of Leprosy","authors":"Rhana Berto da Silva Prata, M. G. M. Barbosa, B. Silva, Jéssica Araújo da Paixão de Oliveira, Tamiris Lameira Bittencourt, R. Pinheiro","doi":"10.5772/INTECHOPEN.88754","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.88754","url":null,"abstract":"Leprosy is a chronic infectious disease caused by the intracellular pathogen Mycobacterium leprae . The disease may present different clinical forms depending on the immunological status of the host. M. leprae may infect macrophages and Schwann cells, and recent studies have demonstrated that macrophages are funda-mental cells for determining the outcome of the disease. Skin lesions from patients with the paucibacillary form of the disease present a predominance of macrophages with a pro-inflammatory phenotype (M1), whereas skin lesions of multibacillary patients present a predominance of anti-inflammatory macrophages (M2). More recently, it was shown that autophagy is responsible for the control of bacillary load in paucibacillary macrophages and that the blockade of autophagy is involved in the onset of acute inflammatory reactional episodes in multibacillary cells. So, strategies that aim to induce autophagy in infected macrophages are promising not only to improve the efficacy of multidrug therapy (MDT) but also to avoid the occurrence of reactional episodes that are responsible for the disabilities observed in leprosy patients.","PeriodicalId":126515,"journal":{"name":"Macrophage Activation - Biology and Disease","volume":"80 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133819304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-18DOI: 10.5772/intechopen.88013
Vijay Kumar
Macrophages are ubiquitously present innate immune cells in humans and animals belonging to both invertebrates and vertebrates. These cells were first recognized by Elia Metchnikoff in 1882 in the larvae of starfish upon insertion of thorns of tangerine tree and later in Daphnia magna or common water flea infected with fungal spores as cells responsible for the process of phagocytosis of foreign particles. Elia Metchnikoff received the Noble prize (Physiology and Medicine) for his discovery and describing the process of phagocytosis in 1908. More than 130 years have passed and different subtypes and roles of macrophages as innate immune cells have been established by the researchers. In addition to their immunoregulatory role in immune homeostasis and pathogenic infection, they also play a crucial role in the pathogenesis of sterile inflammatory conditions including autoimmunity, obesity, and cancer. The present chapter describes the immunoregulatory role of macrophages in the homeostasis and inflammatory diseases varying from autoimmunity to metabolic diseases including obesity.
{"title":"Macrophages: The Potent Immunoregulatory Innate Immune Cells","authors":"Vijay Kumar","doi":"10.5772/intechopen.88013","DOIUrl":"https://doi.org/10.5772/intechopen.88013","url":null,"abstract":"Macrophages are ubiquitously present innate immune cells in humans and animals belonging to both invertebrates and vertebrates. These cells were first recognized by Elia Metchnikoff in 1882 in the larvae of starfish upon insertion of thorns of tangerine tree and later in Daphnia magna or common water flea infected with fungal spores as cells responsible for the process of phagocytosis of foreign particles. Elia Metchnikoff received the Noble prize (Physiology and Medicine) for his discovery and describing the process of phagocytosis in 1908. More than 130 years have passed and different subtypes and roles of macrophages as innate immune cells have been established by the researchers. In addition to their immunoregulatory role in immune homeostasis and pathogenic infection, they also play a crucial role in the pathogenesis of sterile inflammatory conditions including autoimmunity, obesity, and cancer. The present chapter describes the immunoregulatory role of macrophages in the homeostasis and inflammatory diseases varying from autoimmunity to metabolic diseases including obesity.","PeriodicalId":126515,"journal":{"name":"Macrophage Activation - Biology and Disease","volume":"109 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134249690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-09DOI: 10.5772/INTECHOPEN.86474
Joseph L. Roberts, P. Fallon, E. Hams
Obesity is a prevalent condition with several associated co-morbidities including the development of metabolic diseases. In obesity there is immune cell infiltration into the white adipose tissue and this is associated with the generation of inflammation and insulin resistance (IR). A large majority of the infiltrating leukocytes in obese adipose tissue are pro-inflammatory macrophages, which upon activation induce a switch in metabolism from oxidative phosphorylation, as is utilised by macrophages in lean adipose tissue, towards aerobic glycolysis. The signalling pathways evoked in the recruited macrophages induce the release of pro-inflammatory cytokines, in signalling pathways which directly interfere with insulin signalling and thus induce a state of IR. As macrophages appear to play such a pivotal role in the generation of IR and are the largest leukocyte population in the adipose tissue, they provide a promising therapeutic target. Indeed, there are several strategies currently being studied to induce a ‘switch’ in macrophages associated with obese adipose tissue, towards the phenotype of those associated with lean adipose tissue, with arguably the most promising being those strategies designed to target the metabolic pathways within the macrophages. This chapter will discuss the polarisation and activation of macrophages within lean and obese adipose tissue and how these cells can be targeted therapeutically.
{"title":"The Pivotal Role of Macrophages in Metabolic Distress","authors":"Joseph L. Roberts, P. Fallon, E. Hams","doi":"10.5772/INTECHOPEN.86474","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.86474","url":null,"abstract":"Obesity is a prevalent condition with several associated co-morbidities including the development of metabolic diseases. In obesity there is immune cell infiltration into the white adipose tissue and this is associated with the generation of inflammation and insulin resistance (IR). A large majority of the infiltrating leukocytes in obese adipose tissue are pro-inflammatory macrophages, which upon activation induce a switch in metabolism from oxidative phosphorylation, as is utilised by macrophages in lean adipose tissue, towards aerobic glycolysis. The signalling pathways evoked in the recruited macrophages induce the release of pro-inflammatory cytokines, in signalling pathways which directly interfere with insulin signalling and thus induce a state of IR. As macrophages appear to play such a pivotal role in the generation of IR and are the largest leukocyte population in the adipose tissue, they provide a promising therapeutic target. Indeed, there are several strategies currently being studied to induce a ‘switch’ in macrophages associated with obese adipose tissue, towards the phenotype of those associated with lean adipose tissue, with arguably the most promising being those strategies designed to target the metabolic pathways within the macrophages. This chapter will discuss the polarisation and activation of macrophages within lean and obese adipose tissue and how these cells can be targeted therapeutically.","PeriodicalId":126515,"journal":{"name":"Macrophage Activation - Biology and Disease","volume":"21 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114043832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-07-04DOI: 10.5772/INTECHOPEN.86433
Suborno Jati, M. Sen
Infection with pathogenic microbes is a global threat. Macrophages play a fundamental role in promoting host resistance to deadly infections from pathogenic microbes by virtue of a well-orchestrated immune defense system. Phagocytosis and obliteration of invading pathogens by macrophages are an innate immune function that not only sustains immune homeostasis but also bolsters adaptive immune response through antigen processing and presentation. Wnt signaling, where Wnt, a secreted glycoprotein which interacts with Frizzled and ROR cell surface receptors to initiate cellular interactions, could be vital for the immune response executed and propagated by macrophages in both innate and adaptive immune responses. The goal of this chapter is to describe how Wnt signaling influences phagocytosis, autophagy, and transcriptional activation to enable the macrophage to exercise its immune response program to resist infection.
{"title":"Wnt Signaling Regulates Macrophage Mediated Immune Response to Pathogens","authors":"Suborno Jati, M. Sen","doi":"10.5772/INTECHOPEN.86433","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.86433","url":null,"abstract":"Infection with pathogenic microbes is a global threat. Macrophages play a fundamental role in promoting host resistance to deadly infections from pathogenic microbes by virtue of a well-orchestrated immune defense system. Phagocytosis and obliteration of invading pathogens by macrophages are an innate immune function that not only sustains immune homeostasis but also bolsters adaptive immune response through antigen processing and presentation. Wnt signaling, where Wnt, a secreted glycoprotein which interacts with Frizzled and ROR cell surface receptors to initiate cellular interactions, could be vital for the immune response executed and propagated by macrophages in both innate and adaptive immune responses. The goal of this chapter is to describe how Wnt signaling influences phagocytosis, autophagy, and transcriptional activation to enable the macrophage to exercise its immune response program to resist infection.","PeriodicalId":126515,"journal":{"name":"Macrophage Activation - Biology and Disease","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130229395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-05-29DOI: 10.5772/INTECHOPEN.86484
Yuanjun Lu, H. Tan, Ning Wang, Yibin Feng
Macrophage polarization is a spectrum of phenotypes and generally can be classified into two states: (1) classically activated or M1 macrophages, which can be driven by lipopolysaccharide (LPS) alone or in association with Th1 cytokines and produce pro-inflammatory cytokines such as TNF- α , IL-6 and, IL-12, and (2) alternatively activated M2 macrophages, which can be promoted by Th2 mediators IL-4 and IL-13 and produce anti-inflammatory cytokines such as TGF- β and IL-10. Current studies have found that the phenotypic switch between M1 and M2 macrophages governs the fate of an organ in inflammation or injury. The imbalance of M1/M2 polarization is closely involved in various pathological processes and is becoming a potential target for therapeutic strategies. Traditional Chinese medicine is an integrated healthcare system composed of many practices and is characterized by multi-target, multi-level, and coordinated intervention effects. Chinese medicines nowadays are applied to regulate phenotype polarization of macrophages to improve the microenvironment, thus ameliorating or even eliminating the symp-toms. In this chapter, we will discuss the molecular mechanisms of macrophage polarization, their roles in health and disease, and the intervention with Chinese medicines to modulate the polarization of macrophages in tumor microenvironment (TME) for therapeutic purpose.
{"title":"Polarization of Tumor-Associated Macrophages by Chinese Medicine Intervention: Mechanisms and Applications","authors":"Yuanjun Lu, H. Tan, Ning Wang, Yibin Feng","doi":"10.5772/INTECHOPEN.86484","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.86484","url":null,"abstract":"Macrophage polarization is a spectrum of phenotypes and generally can be classified into two states: (1) classically activated or M1 macrophages, which can be driven by lipopolysaccharide (LPS) alone or in association with Th1 cytokines and produce pro-inflammatory cytokines such as TNF- α , IL-6 and, IL-12, and (2) alternatively activated M2 macrophages, which can be promoted by Th2 mediators IL-4 and IL-13 and produce anti-inflammatory cytokines such as TGF- β and IL-10. Current studies have found that the phenotypic switch between M1 and M2 macrophages governs the fate of an organ in inflammation or injury. The imbalance of M1/M2 polarization is closely involved in various pathological processes and is becoming a potential target for therapeutic strategies. Traditional Chinese medicine is an integrated healthcare system composed of many practices and is characterized by multi-target, multi-level, and coordinated intervention effects. Chinese medicines nowadays are applied to regulate phenotype polarization of macrophages to improve the microenvironment, thus ameliorating or even eliminating the symp-toms. In this chapter, we will discuss the molecular mechanisms of macrophage polarization, their roles in health and disease, and the intervention with Chinese medicines to modulate the polarization of macrophages in tumor microenvironment (TME) for therapeutic purpose.","PeriodicalId":126515,"journal":{"name":"Macrophage Activation - Biology and Disease","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126968477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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