Microglial Morphology Across Distantly Related Species: Phylogenetic, Environmental and Age Influences on Microglia Reactivity and Surveillance States.

Dario Carvalho‐Paulo ,Sinara Franco Freitas,Nivin Mazen Said,Renata Rodrigues Dos Reis,Daniel Guerreiro Diniz,Cristovam Wanderley Picanço Diniz,Dora Brites,Zaire Alves Dos Santos,Camila Mendes De Lima,Mauro André Damasceno De Melo,Carlos Santos Filho,Giovanni Freitas Gomes,Nara Gyzely De Morais Magalhães,Cristovam Guerreiro Diniz,Pedro Fernando Da Costa Vasconcelos,Lucas Silva De Siqueira,Aline Andrade De Sousa,Ediely Pereira Henrique,Marcus Augusto De Oliveira,Daniel C Anthony ,David F Sherry ,Patrick Douglas Corrêa Pereira ,José Antônio Picanço Diniz ,Márcia Consentino Kronka Sosthenes ,João Bento-Torres ,Thaís Cristina Galdino De Oliveira

doi:10.3389/fimmu.2021.683026

Abstract

Microglial immunosurveillance of the brain parenchyma to detect local perturbations in homeostasis, in all species, results in the adoption of a spectrum of morphological changes that reflect functional adaptations. Here, we review the contribution of these changes in microglia morphology in distantly related species, in homeostatic and non-homeostatic conditions, with three principal goals (1): to review the phylogenetic influences on the morphological diversity of microglia during homeostasis (2); to explore the impact of homeostatic perturbations (Dengue virus challenge) in distantly related species (Mus musculus and Callithrix penicillata) as a proxy for the differential immune response in small and large brains; and (3) to examine the influences of environmental enrichment and aging on the plasticity of the microglial morphological response following an immunological challenge (neurotropic arbovirus infection). Our findings reveal that the differences in microglia morphology across distantly related species under homeostatic condition cannot be attributed to the phylogenetic origin of the species. However, large and small brains, under similar non-homeostatic conditions, display differential microglial morphological responses, and we argue that age and environment interact to affect the microglia morphology after an immunological challenge; in particular, mice living in an enriched environment exhibit a more efficient immune response to the virus resulting in earlier removal of the virus and earlier return to the homeostatic morphological phenotype of microglia than it is observed in sedentary mice.

Highlights

The processes of microglia extend and retract continuously, guided by its sensome [1], to survey their non-overlapping territorial limits
Our findings in Sapajus apella demonstrated that within the same species and functional area, individual performance in spatial learning and memory tests were highly associated with differential morphology of microglia of the rostral dentate gyrus (DG), but not the CA1 lacunosum molecular layer, suggesting that microglia form and function in this species might be regulated in a tissuespecific fashion
Owing to the tradeoff that exists between neural and immune systems, it has been predicted that larger brains would show less efficient immune responses compared to smaller brains, and that this evolutionary trade-off applies to the innate immune response, but not to the adaptive response one [40]. With this view in mind, we explored the differential response of microglia and neuroinvasion after dengue infection in C. penicillata and M. musculus as proxies for immune capabilities of small and larger brains

Summary

Introduction

The processes of microglia extend and retract continuously, guided by its sensome [1], to survey their non-overlapping territorial limits. To investigate microglia shape changes in a reactive state (non-homeostatic conditions) in small and large brains, we compared M. musculus (unpublished results) and C. penicillata [26] models of antibody-dependent enhancement of dengue disease, and reanalyzed the influences of an exacerbated inflammatory response following a peripheral virus infection on microglia morphological responses of these two species.

Results

Conclusion