Hyung Soon Kim and al. 

Arginase-1 (Arg1) is considered a marker of anti-inflammatory macrophages (M2 macrophages), associated with the resolution of inflammation and the promotion of tissue repair in various pathological conditions. However, its specific role in functional recovery after ischemic stroke remains unknown.

The authors report that, in a photothrombotic murine model of stroke, there is a progressive increase in Arg1 expression, peaking 7 days post-stroke. At this stage, Arg1 is essentially expressed by infiltrating macrophages. A conditional knockout (cKO) of Arg1 in macrophages leads to a significant improvement of motor function, an attenuation of the glial scar and a reduced microglial elimination of synapses in the perilesional cortex. Furthermore, emyelination is also enhanced.

Single-cell RNA-seq analysis reveals a decrease in transforming growth factor β (TGF-β) signaling and a reduced expression of pro-inflammatory cytokine genes in perilesional microglial cells. In vitro experiments based on the co-culture macrophages, microglia and neurons confirm these findings.

Zhangying Cai and al.

One of the major functions of microglia in Alzheimer’s disease (AD) is to contain the spread of plaques composed of amyloid-β (Aβ) aggregates. Recent studies have implicated autophagy-related molecules, particularly ATG7, in this process.

In this study, the authors demonstrate that Atg7 KO microglial cells display an impaired ability to limit the spread of amyloid plaques in a murine model of AD. Single-cell RNA sequencing analysis reveals that Atg7 déficiency reduces the Unfolded Protein Response (UPR), increases oxidative stress and triggers ferroptosis in microglial cells.

Róisín M. McManus and al.

Activation of the NLRP3 inflammasome has been implicated in the pathogenesis of Alzheimer’s disease (AD) via the release of both IL-1β and extracellular ASC complexes ("NLRP3-ASC specks ").

In this study, the authors show that aggregates of amyloid-β peptide activate NLRP3 in APP/PS1 mice, a model that reproduces several characteristics of AD. In these mice, NLRP3 knockout increases glutamine and glutamate metabolism and induces an upregulation of the glutamate transporter Slc1a3. These processes are associated with an improved mitochondrial and metabolic activity in microglial cells. In particular, the production of alpha-ketoglutarate trigger epigenetics modifications and enhances the ability of microglial cells to clear amyloid-β aggregates.

Francisco Javier Rodriguez-Baena and al.

The authors show that microglial activation of the Rela/NF-κB pathway promotes brain metastases in a murine model of melanoma. Targeting this pathway reprograms microglia toward a pro-inflammatory phenotype, enhancing antitumor immunity and reducing brain metastatic burden.

Similarly, in humans, pro-inflammatory microglial markers in melanoma brain metastases are associated with better responses to immune checkpoint inhibitors.

Xiaoting Wu and al.

This study examines the impact of lipid metabolism in Alzheimer’s disease (AD), focusing on the contribution of brain macrophages with high lipid droplets (LDs) contents, particularly microglial cells and border-associated macrophages (BAMs) (i.e. essentially meningeal and perivascular macrophages).

BAMs and activated CD11c+ microglial cells located near amyloid-β plaques exhibit a transcriptomic signature indicative of LD accumulation. Moreover, the authors observe an inverse correlation between intracellular lipid load and microglial phagocytic activity. A genetic model enabling microglial inhibition of LD formation establishes a causative link between poor LD contents and an increased ability to phagocytose amyloid-β aggregates.

Madison R. Mix and al.

The human brain harbors tissue-resident memory CD8+ T cells (TRM) that target viral antigens. However, the impact of repeated peripheral viral infections on the generation, phenotype, localization, and memory functions of brain TRM remains poorly understood.

In this study, the authors investigated two murine models of peripheral viral infection. They show that circulating memory CD8+ T cells, previously exposed to an antigen, exhibit a reduced capacity to form brain TRM compared to naive CD8+ T cells. Moreover, brain TRM subjected to repeated stimulations differentially express inhibitory receptors, retain their functionality, and display distinct localization patterns compared to primary memory T cells.

Despite these differences, repeatedly stimulated brain TRM provide similar protection against intracranial infection, with enhanced recruitment of peripheral lymphocytes during the memory response.

Michael A. Wheeler & Francisco J. Quintana

The nervous and immune systems play complementary roles in shaping the adaptation of organisms to environmental changes. However, the mechanisms underlying the crosstalk between these two systems, known as neuro-immune interactions, remain poorly understood.

This review summarizes recent advances regarding such neuro-immune communications, with a particular focus on the central nervous system (CNS), its response to immune signals, and the effects of its activity on the immune system.