Maternal infection and immune involvement in autism

Abstract

Recent studies have highlighted a connection between infection during pregnancy and the increased risk of autism in the offspring. Parallel studies of cerebral spinal fluid, blood and postmortem brains reveal an ongoing, hyper-responsive inflammatory-like state in many young as well as adult autism subjects. There are also indications of gastrointestinal problems in at least a subset of autistic children. Work on the maternal infection risk factor using animal models indicates that aspects of brain and peripheral immune dysregulation can begin during fetal development and continue through adulthood. The offspring of infected or immune-activated dams also display cardinal behavioral features of autism, as well as neuropathology consistent with that seen in human autism. These rodent models are proving useful for the study of pathogenesis and gene-environment interactions as well as for the exploration of potential therapeutic strategies.

Figure 1. Summary of MIA-induced effects on the placenta

Maternal injection of poly(I:C) activates the maternal immune system, elevating IL-6, which enters the spiral arteries that descend through the decidua and spongiotrophoblast layers, filling the maternal bloodspaces of the labyrinth. Resident immune cells in the decidua are activated to express CD69 and further propagate the inflammatory response. IL-6 produced by decidual cells acts on target cells in the spongiotrophoblast layer. Ligation of the IL-6Ra with gp130 causes JAK/STAT3 activation and increases in acute phase proteins, such as SOCS3, and down-regulation of placental growth hormone (GH) production. This leads to reduced insulin-like growth factor binding protein 3 (IGFBP3) and IGFI. Global changes in STAT3 activation in the spongiotrophoblast layer alter the production of placenta-specific pro-lactin protein (PLP) and other pro-lactin proteins. These various changes in endocrine factors very likely to lead to acute placental pathophysiology and subsequent effects on fetal development. (Reproduced from ref. , with permission.)