Microglia-precursor cell interactions in health and in pathology

Abstract

Until recently, microglia were mainly known as the resident phagocytes of the brain, i.e. the 'immunological warriors' of the brain. However, extensive knowledge is being accumulated about the functions of microglia beyond immunity. Nowadays, it is well accepted that microglial cells are highly dynamic and responsive, and that they intervene in a dual manner in many developmental processes that shape the central nervous system, including neurogenesis, gliogenesis, spatial patterning, synaptic formation and elimination, and neural circuit establishment and maturation.The differentiation and the pool of precursor cells were also shown to be under microglia regulation via bidirectional communication. In this concise review, I discuss our recent work in microglia-Pax6 + cell interactions in one of the circumventricular organs, the pineal gland. An analogy with the rest of the central nervous system is also presented.In addition, I briefly examine mechanisms of interaction between microglia and non-microglial cells in both health and disease. New avenues are also introduced, which may lead us to better comprehend the impact of microglia in physiological and pathological conditions.

Sympathetic Innervation of the Mammalian Pineal Gland: Its Involvement in Ontogeny and Physiology, and in Pineal Dysfunction

“…The PG emerges as an evagination of the roof of the diencephalon, late in the embryonic (E) period (E14-E15 for rat) [8,9]. The basis of pineal morphogenesis, and the dynamic and intricate network of transcription factors (TF) involved in the establishment and maintenance of the pineal phenotype, have been extensively characterized, as well as the consequences of certain gene mutations on these mechanisms [28,[34][35][36][37][38][39]. Cells that are positive for the essential ontogenetic TF Pax6 and the intermediate filament protein vimentin (Vim) are present in the pineal primordium.…”

Maf1 Ameliorates Sepsis-Associated Encephalopathy by Suppressing the NF-kB/NLRP3 Inflammasome Signaling Pathway

“…NF-kB activates a variety of genes in the nucleus, including microglial nod-like receptor protein 3 (NLRP3). NLRP3 plays an important role in the inflammation cascade by amplifying an inflammation response (13); thus, inhibition of NLRP3 inflammasome activity has been proposed as a strategy for treating various diseases, including neurological diseases (14)(15)(16)(17), osteoarthritis (18), diabetic nephropathy (19), liver fibrosis (20). Moreover, NF-kB-induced NLRP3 expression is sufficient for NLRP3 to mediate inflammasome formation, suggesting that blocking the functional cross-talk that occurs between NF-kB and NLRP3 might attenuate an inflammationinduced BBB injury.…”

Editorial: Trends in neuroimmunology: cross-talk between brain-resident and peripheral immune cells in both health and disease

“…Among the interesting contributions, an in vitro study on primary murine glia by Li et al showed differential substratedependent and time-dependent phagocytic behavior and phenotypic plasticity among M0-like (unstimulated), M1-like (pro-inflammatory) and M2-like (anti-inflammatory) microglia subtypes. Although the application of M1/M2 terminology in the microglia field has been dismissed, the coexistence of proinflammatory and anti-inflammatory microglial states has been documented, including in circumventricular organs (9)(10)(11)(12). Li et al differentiated cultured glial cells into M1-like and M2-like microglia subtypes by treating them either with granulocyte colony stimulating factor and interferon-gamma (GM-CSF/IFNg), or with macrophage colony-stimulating factor and interleukin-4 (M-CSF/ IL-4), respectively.…”