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Review
. 2023 Jan 31;24(3):2703.
doi: 10.3390/ijms24032703.

Inflammation and the Potential Implication of Macrophage-Microglia Polarization in Human ASD: An Overview

Nadia Lampiasi  1 , Rosa Bonaventura  1 , Irene Deidda  1 , Francesca Zito  1 , Roberta Russo  1
Affiliations
Review

Inflammation and the Potential Implication of Macrophage-Microglia Polarization in Human ASD: An Overview

Nadia Lampiasi et al. Int J Mol Sci. .

Abstract

Autism spectrum disorder (ASD) is a heterogeneous collection of neurodevelopmental disorders, difficult to diagnose and currently lacking treatment options. The possibility of finding reliable biomarkers useful for early identification would offer the opportunity to intervene with treatment strategies to improve the life quality of ASD patients. To date, there are many recognized risk factors for the development of ASD, both genetic and non-genetic. Although genetic and epigenetic factors may play a critical role, the extent of their contribution to ASD risk is still under study. On the other hand, non-genetic risk factors include pollution, nutrition, infection, psychological states, and lifestyle, all together known as the exposome, which impacts the mother's and fetus's life, especially during pregnancy. Pathogenic and non-pathogenic maternal immune activation (MIA) and autoimmune diseases can cause various alterations in the fetal environment, also contributing to the etiology of ASD in offspring. Activation of monocytes, macrophages, mast cells and microglia and high production of pro-inflammatory cytokines are indeed the cause of neuroinflammation, and the latter is involved in ASD's onset and development. In this review, we focused on non-genetic risk factors, especially on the connection between inflammation, macrophage polarization and ASD syndrome, MIA, and the involvement of microglia.

Keywords: ASD; MIA; cytokines; exposome; innate immune system; macrophage; mast cells; microglia; polarization.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the effects of different exposome factors on MIA, neuroinflammation and immune dysregulation occurring in the period of neurodevelopment.
Figure 2
Figure 2
Schematic representation of the main steps occurring to develop ASD.
Figure 3
Figure 3
Microglia and neuroinflammation. During homeostasis, branching microglia play crucial roles such as surveillance, phagocytosis of debris, synaptic homeostasis, maintenance of neuronal plasticity, and trophic support. Neuroinflammation causes the microglial phenotype to change to an amoeboid state and the release pro-inflammatory cytokines (IL-6, TNFα, IL-1β), with loss of homeostatic functions, synaptic alterations, increased spinal density and neuronal dysfunction.
See this image and copyright information in PMC

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