Distinct Features of Brain-Resident Macrophages: Microglia and Non-Parenchymal Brain Macrophages

Tissue-resident macrophages play an important role in maintaining tissue homeostasis and innate immune defense against invading microbial pathogens. Brain-resident macrophages can be classified into microglia in the brain parenchyma and non-parenchymal brain macrophages, also known as central nervous system-associated or border-associated macrophages, in the brain-circulation interface. Microglia and non-parenchymal brain macrophages, including meningeal, perivascular, and choroid plexus macrophages, are mostly produced during embryonic development, and maintained their population by self-renewal. Microglia have gained much attention for their dual roles in the maintenance of brain homeostasis and the induction of neuroinflammation. In particular, diverse phenotypes of microglia have been increasingly identified under pathological conditions. Single-cell phenotypic analysis revealed that microglia are highly heterogenous and plastic, thus it is difficult to define the status of microglia as M1/M2 or resting/activated state due to complex nature of microglia. Meanwhile, physiological function of non-parenchymal brain macrophages remain to be fully demonstrated. In this review, we have summarized the origin and signatures of brain-resident macrophages and discussed the unique features of microglia, particularly, their phenotypic polarization, diversity of subtypes, and inflammasome responses related to neurodegenerative diseases.     

Macrophages and CNS remyelination

Microglia are the resident macrophages of the central nervous system that survey the microenvironment for signals of injury or infection. The response to such signals induces an inflammatory response involving macrophages derived from both resident microglia and recruited circulating monocytes. Although implicated as contributors to autoimmune‐mediated injury, microglia/ macrophages have recently been shown to be critical for the important central nervous system regenerative process of remyelination. This functional dichotomy may reflect their ability to be polarized along a continuum of activation states including the well‐characterized cytotoxic M1 and regenerative M2 phenotypes. Here, we review the roles of microglia, monocytes and the macrophages which they give rise to in creating lesion environments favourable to remyelination, highlighting the specific roles of M1 and M2 phenotypes and how the pro‐regenerative role of the innate immune system is altered by ageing.

     

Macrophages in rheumatoid arthritis

In rheumatoid arthritis (RA) tissue macrophages release growth factors, matrix metalloproteinases, cytokines, and chemokines. While in normal joints there is a balance between proinflammatory and anti-inflammatory cytokines, an imbalance between these inducers and inhibitors of inflammation occurs in RA, where macrophages are responsible for inducing inflammation, matrix destruction and angiogenesis.     

巨噬细胞与创伤愈合

巨噬细胞是创伤愈合过程中一系列复杂反应中的关键环节,它调节成纤维细胞和血管内皮细胞的生物学活性,在创伤愈合过程中占有不可替代的作用。加强巨噬细胞功能和应用细胞因匀能有效地促进创伤愈合。     

Macrophages express glial markers

We have investigated the relationships between the glial cells of the central nervous system and the resident macrophages. The data reported here show that mouse peritoneal, bone marrow and spleen macrophages are immunoreactive to antibodies specific for astrocytes and oligodendrocytes.     

Macrophages in Pacinian corpuscles

The presence of macrophages in the outer bulb region of mouse, monkey and human Pacinian corpuscles was demonstrated by light and electron microscopy. In the normal, nontreated, Pacinian corpuscles, a few particular cells were located in the spaces between lamellae of the outer bulb. These cells contained numerous vesicles and vacuoles, and various cytoplasmic processes. When horseradish peroxidase (HRP) was injected locally or systemically, many HRP-positive cells, which were considered to be similar to the particular cells described above, were found in the outer bulb region of the corpuscles. Electron microscopy revealed that these cells contained HRP in vesicles and vacuoles, suggesting that they were macrophages vigorously taking up exogenous HRP. Macrophages in the Pacinian corpuscles are considered to work as scavengers to keep the inner environment of the corpuscles clear and constant with regard to its macromolecular content.     

Macrophages in rheumatoid arthritis

The abundance and activation of macrophages in the inflamed synovial membrane/pannus significantly correlates with the severity of rheumatoid arthritis (RA). Although unlikely to be the 'initiators' of RA (if not as antigen-presenting cells in early disease), macrophages possess widespread pro-inflammatory, destructive, and remodeling capabilities that can critically contribute to acute and chronic disease. Also, activation of the monocytic lineage is not locally restricted, but extends to systemic parts of the mononuclear phagocyte system. Thus, selective counteraction of macrophage activation remains an efficacious approach to diminish local and systemic inflammation, as well as to prevent irreversible joint damage.     

SIV Infection of Lung Macrophages

HIV-1 depletes CD4+ T cells in the blood, lymphatic tissues, gut and lungs. Here we investigated the relationship between depletion and infection of CD4+ T cells in the lung parenchyma. The lungs of 38 Indian rhesus macaques in early to later stages of SIVmac251 infection were examined, and the numbers of CD4+ T cells and macrophages plus the frequency of SIV RNA+ cells were quantified. We showed that SIV infected macrophages in the lung parenchyma, but only in small numbers except in the setting of interstitial inflammation where large numbers of SIV RNA+ macrophages were detected. However, even in this setting, the number of macrophages was not decreased. By contrast, there were few infected CD4+ T cells in lung parenchyma, but CD4+ T cells were nonetheless depleted by unknown mechanisms. The CD4+ T cells in lung parenchyma were depleted even though they were not productively infected, whereas SIV can infect large numbers of macrophages in the setting of interstitial inflammation without depleting them. These observations point to the need for future investigations into mechanisms of CD4+ T cell depletion at this mucosal site, and into mechanisms by which macrophage populations are maintained despite high levels of infection. The large numbers of SIV RNA+ macrophages in lungs in the setting of interstitial inflammation indicates that lung macrophages can be an important source for SIV persistent infection.