Topic: macrophages

We are interested in the biology of macrophages, which represent the first line of defense against pathogens. In Drosophila, the embryonic hemocytes arise from the mesoderm whereas glial cells arise from multipotent precursors in the neurogenic region. These cell types represent, respectively, the macrophages located outside and within the nervous system (similar to vertebrate microglia). Thus, despite their different origin, hemocytes and glia display common functions. In addition, both cell types express the Glide/Gcm transcription factor, which plays an evolutionarily conserved role as an a

Genome-wide association studies and functional genomics studies have linked specific cell types, genes, and pathways to Alzheimer’s disease (AD) risk. In particular, AD risk alleles primarily affect the abundance or structure, and thus the activity, of genes expressed in macrophages, strongly implicating microglia (the brain-resident macrophages) in the etiology of AD. These genes converge on pathways (endocytosis/phagocytosis, cholesterol metabolism, and immune response) with critical roles in core macrophage functions such as efferocytosis. Here, we review these pathways, highlighting releva

Inflammation is a key component of the innate immune response. Primarily designed to remove noxious agents and limit their detrimental effects, the prolonged and/or inappropriately scaled innate immune response may be detrimental to the host and lead to a chronic disease. Indeed, there is increasing evidence suggesting that a chronic deregulation of immunity may represent one of the key elements in the pathobiology of many brain disorders. Microglia are the principal immune cells of the brain. The consensus today is that once activated microglia/macrophages can acquire a wide repertoire of pro

Carnosine is a natural dipeptide widely distributed in mammalian tissues and exists at particularly high concentrations in skeletal and cardiac muscles and brain. A growing body of evidence shows that carnosine is involved in many cellular defense mechanisms against oxidative stress, including inhibition of amyloid-β (Aβ) aggregation, modulation of nitric oxide (NO) metabolism, and scavenging both reactive nitrogen and oxygen species. Different types of cells are involved in the innate immune response, with macrophage cells representing those primarily activated, especially under different dis

Glioblastomas (GB) are the most malignant primary brain tumors with median survival of about 17 month despite extensive treatment. Molecular heterogeneity and the tumor microenvironment contribute to the challenges in treating GBs. Glioma-associated microglia and macrophages, comprising 30-50% of non-neoplastic cells in the microenvironment, play a crucial role in facilitating tumor growth and inducing tissue necrosis. However, the intricate interplay between these immune and glioma cells remains poorly understood.This study focuses on understanding the dynamic role of microglia during gliobla

Alzheimer's disease is the most prevalent form of dementia in elderly, presenting a significant global public health challenge. Its pathological hallmarks include extracellular amyloid β (Aβ) aggregates or senile plaques, intracellular neurofibrillary tangles, and inflammatory processes. Despite recent therapeutic approvals targeting Aβ, controversies persist regarding their efficacy. Our goal is to determine the biological impact of molecules that inhibit various steps of Alzheimer's development, which could potentially be integrated into complex treatment regimens in the future. To this end,

N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is a neurological disorder mediated by autoantibodies targeting the NMDAR. Patients’ autoantibodies are pathogenic, as they cause neuronal dysfunction in vitro, and molecular and behavioral changes in mouse models of cerebroventricular transfer of patients’ antibodies. Active immunization models have confirmed these effects and informed on the development of adaptive immune responses. Here we aimed to characterize the accompanying innate immune response and how this contributes to disease pathogenesis. Female C57BL/6 mice were immunized with N

Vincristine (VCR), an anticancer drug, frequently causes chemotherapy-induced peripheral neuropathy (CIPN). We have reported that macrophages (Mφ)-derived HMGB1 is involved in CIPN induced by paclitaxel in mice, whereas the mechanisms for VCR-induced CIPN (VIPN) remain unclear. We thus examined whether VIPN involves HMGB1 derived from Mφ or Schwann cells in mice. VCR at 0.2 mg/kg was administrated i.p. to mice daily for 10 days with a 2-day break, and nociceptive threshold at the hindpaw was evaluated by von Frey test. An anti-HMGB1-neutralizing antibody (HMGB1-Ab), soluble thrombomodulin (TMα

The choroid plexus (ChP) is a highly vascularized non-neural tissue located in the brain ventricles and is responsible for the production of a large part of the cerebrospinal fluid (CSF). In addition, the epithelial cells of the ChP synthesize neurotrophic factors and other signalling molecules into CSF and act as a blood-cerebrospinal fluid barrier. Importantly, ChP cells harbour a robust circadian oscillator that may control ChP function and may play an important role in the circuitry between brain clocks. In this study, we aimed to find out whether the ChP clock is sensitive to a robust imm

The kynurenine pathway of tryptophan metabolism is an important regulator of CNS neuroglial activity and immune system function. Here, novel factors influencing the kynurenine pathway (KP) are presented, with preliminary data examining links with TNF, a mediator known to have substantial clinical relevance. Bone-marrow derived macrophages (BMDMs), THP-1 and, RAW264.7 lines and mice lacking TNF receptor 1 (TNFR1) were used. Gene expression was assessed by qRT-PCR. Results showed that the bacterial serine protease subtilisin and mammalian prostate specific antigen (PSA) induced expression of IDO

Friedreich ataxia (FA), the most common recessive hereditary ataxia, is an early-onset neurodegenerative disease characterized by pathological changes occurring first in the peripheral dorsal root ganglia (DRG), with loss of the large sensory proprioceptive neurons, leading to ganglionopathy and proprioceptive deficits. FA is caused by a mutation in frataxin gene (Fxn), leading to reduced expression of frataxin protein (FXN), an essential ubiquitous mitochondrial protein. Most research has focused on the pathophysiological involvement of proprioceptors. However, in recent years, neuroinflammat

Aims. Interleukin-33 is a protein enhancing Th2 cytokine production, initially described as an alarmin that is released from dying, necrotic cells to affect the immune response. Therefore, we aimed to examine the role of IL-33 in response to both CNS and PNS injury. Methods and Results. Using qPCR, Western blotting, and ELISA assay we showed significant up-regulation of IL-33 in two models of nervous system pathology in response to demyelination of the CNS white matter and sciatic nerve crush. We showed that IL-33 is produced exclusively by non-myelinating oligodendrocytes in the intact white

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse reactions in chemotherapy with cytotoxic anticancer agents. We have demonstrated that CIPN caused by paclitaxel involves high mobility group box 1 (HMGB1), a nuclear protein, derived from macrophages (Mφ) in laboratory animals (Neuropharmacology 141, 201, 2018), and that postmenopausal estrogen decline aggravates CIPN in patients undergoing paclitaxel-based chemotherapy (J Pharmacol Sci 146, 49, 2021). In this study, we analyzed estrogen modulation of upstream and downstream mechanisms of HMGB1. Female mice were subje

While several studies have presented evidence that both mouse and human adult cortical astrocytes can dedifferentiate and form multipotent neurospheres after brain injury, other observations support that these neurospheres are formed by astroglia progenitors derived from subependymal zone (SEZ) resident neural stem cells which migrated to the cortex. In this study, we developed a new gliosis culture model composed by cells from the injured cortex, including reactive astrocytes, microglia, macrophages, and NG2 cells that mimic some characteristics of the injured brain but in a more controlled l

Peritonitis poses a serious medical challenge due to abdominal wall inflammation, often triggered by infectious agents. Understanding its immunological mechanisms is crucial for innovative therapies. The regulatory peptide galanin and its receptors (GAL1-3-R) are expressed on various immune cells and play pivotal roles in inflammation. The impact of GAL2/3-R knockout (KO) was assessed in a preclinical peritonitis model, using aged 4% thioglycollate medium (TGM) injected intraperitoneally in GAL2/3-R KO and corresponding WT mice. Comparison to vehicle controls was included to discern treatment-

Experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis, is triggered by myelin-specific T effector cells primed in peripheral lymph nodes that migrate to the central nervous system (CNS) where they are reactivated and induce demyelination. First-line treatment for disease relapses is a high dose of glucocorticoids for five consecutive days. Although melatonin ameliorates the severity of EAE by modulating T-cell responses, its action mechanism remains unclear. Our objective was to study the effects of melatonin on the peripheral priming of T cells, their migratio