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

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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
    Africa Health Research Institute, K-Rith Tower Building, Nelson Mandela School of Medicine, Durban 4001, South Africa
    Department of Microbiology, University of Alabama, Birmingham, AL 35294, USA)

  • 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)

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-α), interferon (IFN)-γ and IL-1β 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.

Suggested Citation

  • Wadzanai Manjeese & Nontobeko E. Mvubu & Adrie J. C. Steyn & Thabisile Mpofana, 2021. "Mycobacterium tuberculosis -Induced Maternal Immune Activation Promotes Autism-Like Phenotype in Infected Mice Offspring," IJERPH, MDPI, vol. 18(9), pages 1-13, April.
    • Handle: RePEc:gam:jijerp:v:18:y:2021:i:9:p:4513-:d:542468
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    References listed on IDEAS

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    1. Noor B. Almandil & Deem N. Alkuroud & Sayed AbdulAzeez & Abdulla AlSulaiman & Abdelhamid Elaissari & J. Francis Borgio, 2019. "Environmental and Genetic Factors in Autism Spectrum Disorders: Special Emphasis on Data from Arabian Studies," IJERPH, MDPI, vol. 16(4), pages 1-16, February.
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