Mycobacterium tuberculosis -Induced Maternal Immune Activation Promotes Autism-Like Phenotype in Infected Mice Offspring

Wadzanai Manjeese, Nontobeko E. Mvubu, Adrie J. C. Steyn and Thabisile Mpofana
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Wadzanai Manjeese: Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu Natal, Durban 4001, South Africa
Nontobeko E. Mvubu: Discipline of Microbiology, School of Life Sciences, College of Agriculture, Engineering and Science, University of KwaZulu Natal, Durban 4001, South Africa
Adrie J. C. Steyn: Discipline of Microbiology, School of Life Sciences, College of Agriculture, Engineering and Science, University of KwaZulu Natal, Durban 4001, South Africa
Thabisile Mpofana: Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu Natal, Durban 4001, South Africa

IJERPH, 2021, vol. 18, issue 9, 1-13

Abstract: The maternal system’s exposure to pathogens during pregnancy influences fetal brain development causing a persistent inflammation characterized by elevated pro-inflammatory cytokine levels in offspring. Mycobacterium tuberculosis ( Mtb ) is a global pathogen that causes tuberculosis, a pandemic responsible for health and economic burdens. Although it is known that maternal infections increase the risk of autism spectrum disorder (ASD), it is not known whether Mtb infection is sufficient to induce ASD associated behaviors, immune dysregulation and altered expression of synaptic regulatory genes. The current study infected pregnant Balb/c mice with Mtb H37Rv and valproic acid (VPA) individually and in combination. Plasma cytokine profiles were measured in offspring using the Bio-plex Th17 pro mouse cytokine panel. Mtb infection increased plasma interleukin (IL)-6 and IL-17A, while tumor necrosis factor alpha (TNF-?), interferon (IFN)-? and IL-1? were reduced when compared with saline. Mtb -induced maternal immune activation (MIA) offspring displayed increased grooming behavior. The study also revealed dysregulation in gene expression of synaptic molecules in the cerebellum. MIA rescued the VPA-induced effects on self-grooming and social interaction behaviors. Our finding therefore highlights a potential role of Mtb as a MIA agent that can potentially contribute to ASD.

Keywords: maternal immune activation; Mycobacterium tuberculosis; cytokines; social behaviors; Autism; synaptic genes; restrictive repetitive patterns (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2021
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