Abstract
In this study, we confirmed that the number of resident homeostatic microglia increases during chronic Toxoplasma gondii infection. Given that the progression of Alzheimer’s disease (AD) worsens with the accumulation of amyloid β (Aβ) plaques, which are eliminated through microglial phagocytosis, we hypothesized that T. gondii-induced microglial proliferation would reduce AD progression. Therefore, we investigated the association between microglial proliferation and Aβ plaque burden using brain tissues isolated from 5XFAD AD mice (AD group) and T. gondii-infected AD mice (AD + Toxo group). In the AD + Toxo group, amyloid plaque burden significantly decreased compared with the AD group; conversely, homeostatic microglial proliferation, and number of plaque-associated microglia significantly increased. As most plaque-associated microglia shifted to the disease-associated microglia (DAM) phenotype in both AD and AD + Toxo groups and underwent apoptosis after the lysosomal degradation of phagocytosed Aβ plaques, this indicates that a sustained supply of homeostatic microglia is required for alleviating Aβ plaque burden. Thus, chronic T. gondii infection can induce microglial proliferation in the brains of mice with progressed AD; a sustained supply of homeostatic microglia is a promising prospect for AD treatment.
Highlights
Microglia are resident macrophages of the central nervous system (CNS), constitute 5–10% of total brain cells, maintain CNS homeostasis, and protect the CNS by phagocytosing pathogens [1,2,3,4]
To investigate the proliferation of homeostatic microglia, the TMEM119 antibody was used for staining resident homeostatic microglia through the immunofluorescence assay (IFA); CD11b and Iba1 co-staining was used for activated microglia (Figure 1C,D)
Our findings revealed that chronic T. gondii infection in the brain induced M1-type activation of microglia through the continuous proliferation of homeostatic microglia
Summary
Microglia are resident macrophages of the central nervous system (CNS), constitute 5–10% of total brain cells, maintain CNS homeostasis, and protect the CNS by phagocytosing pathogens [1,2,3,4]. T. gondii infection induces the expression of anti-inflammatory cytokines and negative regulators of toxoplasmic encephalitis, namely suppressor of cytokine signaling 1 (SOCS1) and Arg, to reduce the inflammatory response [8,9]. We demonstrated that neuroinflammation was suppressed and homeostasis restored by increasing anti-inflammatory cytokine production in the state of disease-associated inflammatory response [8,9]. Given that microglia continuously monitor the surrounding parenchyma to sense alterations in brain function and are involved in controlling neuronal excitability, synaptic activity, neurogenesis, and clearance of apoptotic cells in the healthy adult brain [10], it would be interesting to determine how microglia affect chronic neurodegenerative diseases, such as AD, after T. gondii infection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
