Microglia are involved in phagocytosis and extracellular digestion during Zika virus encephalitis in young adult immunodeficient mice.

TitleMicroglia are involved in phagocytosis and extracellular digestion during Zika virus encephalitis in young adult immunodeficient mice.
Publication TypeJournal Article
Year of Publication2021
AuteursEnlow, W, Bordeleau, M, Piret, J, Ibáñez, FGonzález, Uyar, O, Venable, M-C, Goyette, N, Carbonneau, J, Tremblay, M-È, Boivin, G
JournalJ Neuroinflammation
Date Published2021 Aug 16
KeywordsAnimals, Brain, Mice, Microglia, Neurons, Phagocytosis, Zika Virus Infection

BACKGROUND: Zika virus (ZIKV) has been associated with several neurological complications in adult patients.METHODS: We used a mouse model deficient in TRIF and IPS-1 adaptor proteins, which are involved in type I interferon production, to study the role of microglia during brain infection by ZIKV. Young adult mice were infected intravenously with the contemporary ZIKV strain PRVABC59 (1 × 10 PFUs/100 µL).RESULTS: Infected mice did not present overt clinical signs of the disease nor body weight loss compared with noninfected animals. However, mice exhibited a viremia and a brain viral load that were maximal (1.3 × 10 genome copies/mL and 9.8 × 10 genome copies/g of brain) on days 3 and 7 post-infection (p.i.), respectively. Immunohistochemistry analysis showed that ZIKV antigens were distributed in several regions of the brain, especially the dorsal hippocampus. The number of Iba1/TMEM119 microglia remained similar in infected versus noninfected mice, but their cell body and arborization areas significantly increased in the stratum radiatum and stratum lacunosum-moleculare layers of the dorsal hippocampus cornu ammoni (CA)1, indicating a reactive state. Ultrastructural analyses also revealed that microglia displayed increased phagocytic activities and extracellular digestion of degraded elements during infection. Mice pharmacologically depleted in microglia with PLX5622 presented a higher brain viral load compared to untreated group (2.8 × 10 versus 8.5 × 10 genome copies/g of brain on day 10 p.i.) as well as an increased number of ZIKV antigens labeled with immunogold in the cytoplasm and endoplasmic reticulum of neurons and astrocytes indicating an enhanced viral replication. Furthermore, endosomes of astrocytes contained nanogold particles together with digested materials, suggesting a compensatory phagocytic activity upon microglial depletion.CONCLUSIONS: These results indicate that microglia are involved in the control of ZIKV replication and/or its elimination in the brain. After depletion of microglia, the removal of ZIKV-infected cells by phagocytosis could be partly compensated by astrocytes.

Alternate JournalJ Neuroinflammation
PubMed ID34399779
PubMed Central IDPMC8369691
Grant List148361 / CAPMC / CIHR / Canada
353750 / CAPMC / CIHR / Canada
RGPIN-2014-0508 / / Natural Sciences and Engineering Research Council of Canada /