Fig. 3

TMEM119⁺ microglia/microglial-like cells exhibit impaired functions, including reduced phagocytic activity in highly infected thalamus. a HSV-1-infected thalamus was labeled with antibodies against TMEM-119 (green), CD68 (red), HSV-1 (white), and counterstained with DAPI (blue). (left) Highly infected thalamus immunostained with TMEM119 (green), CD68 (red), HSV-1 (white) antibodies, and counterstained with DAPI showed increased numbers of TMEM119⁻/CD68⁺ cells in close/direct contact with HSV-1⁺ CNS cells (white arrow) on day 6 p.i.. (right) Confocal microscopy image shows TMEM119⁺ ameboid microglia/microglia-like cells (white arrow) with the lack of CD68 expression. HSV-1 signal was colocalized with TMEM119⁺/CD68⁻ ramified (white circle) and ameboid microglia/microglia-like cells (white arrow), suggesting an impaired phagocytic activity following microglial infection by HSV-1 or the phagocytosis of HSV-1⁺ CNS cells. b (1, 2) Representative pictures at day (1) 0 and (2) 6 p.i. showed that on day 6 p.i. microglia/microglial-like cells have a lower number of (3) immature lysosomes without major changes in (4) mature and (5) total lysosomes number and made fewer contacts with (6) myelinated axons and (7) degraded myelin. (1, 2) Microglia/microglial-like cell organelles and elements of their microenvironment that are in contact with the cell body are pseudocolored; immature lysosomes are in yellow, mature lysosomes are in orange, lipofuscins are in pink, lipid bodies are in dark purple, myelinated axons are in blue, presynaptic axon terminals are in light green, and postsynaptic dendrites or dendritic spines are in dark green. Myelin degradation is distinguished by a white asterisk (*). Apparent cell bodies are identified by a capital letter, where “M” stands for microglia/microglial-like cell, and “A” stands for astrocytes. Scale bars are equivalent to 5 µm. (3–7) Graphs show means (thin wide bar) ± SEM, where individual values are represented by dark gray circles at day 0 (uninfected control) and black diamonds at day 6 p.i.