Distinct trans-placental effects of maternal immune activation by TLR3 and TLR7 agonists: implications for schizophrenia risk
Autor: | Maria Suessmilch, Alison McColl, Jaedeok Kwon, Brian J. Morris, Jonathan Cavanagh |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Male
Chemokine medicine.medical_specialty Offspring medicine.medical_treatment Science Placenta Virus Article chemistry.chemical_compound Mice Pregnancy Internal medicine Medicine Animals Multidisciplinary Membrane Glycoproteins biology business.industry Interleukin-6 Tumor Necrosis Factor-alpha Imidazoles TLR7 Toll-Like Receptor 3 Mice Inbred C57BL Endocrinology Cytokine medicine.anatomical_structure chemistry Toll-Like Receptor 7 Prenatal Exposure Delayed Effects TLR3 biology.protein Schizophrenia Female Resiquimod Chemokines business Neuroscience |
Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) |
ISSN: | 2045-2322 |
Popis: | Exposure to infection in utero predisposes towards psychiatric diseases such as autism, depression and schizophrenia in later life. The mechanisms involved are typically studied by administering mimetics of double-stranded (ds) RNA viral or bacterial infection to pregnant rats or mice. The effect of single-stranded (ss) virus mimetics has been largely ignored, despite evidence linking prenatal ss virus exposure specifically with psychiatric disease. Understanding the effects of gestational ss virus exposure has become even more important with the current SARS-CoV-2 pandemic. In this study, in pregnant mice, we compare directly the effects, on the maternal blood, placenta and the embryonic brain, of maternal administration of ds-virus mimetic poly I:C (to activate toll-like receptor 3, TLR3) and ss-virus mimetic resiquimod (to activate TLR7/8). We find that, 4h after the administration, both poly I:C and resiquimod elevated the levels of IL-6, TNFα, and chemokines including CCL2 and CCL5, in maternal plasma. Both agents also increased placental mRNA levels of IL-6 and IL-10, but only resiquimod increased placental TNFα mRNA. In foetal brain, poly I:C produced no detectable immune-response-related increases, whereas pronounced increases in cytokine (e.g. Il-6, Tnfα) and chemokine (e.g. Ccl2, Ccl5) expression were observed with maternal resiquimod administration. The data show substantial differences between the effect of maternal exposure to a TLR7/8 activator as compared to a TLR3 activator. There are significant implications for future modelling of diseases where maternal ss virus exposure contributes to environmental disease risk in offspring. |
Databáze: | OpenAIRE |
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