Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior

Humann, Jessica; Mann, Beth; Gao, Geli; Moresco, Philip; Ramahi, Joseph S.; Loh, Lip Nam; Farr, A.; Hu, Yi; Durick-Eder, Kelly; Fillon, Sophie; Smeyne, Richard J.; Tuomanen, Elaine

doi:10.1016/j.chom.2016.05.017

Cited by 32 publications

(20 citation statements)

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“…The results showed that there were very few CC3 + cells present in the developing neocortex (Additional file 2 : Figure S1A–E). MIA increased the concentrations of CC3 and PCNA in fetal cortex at E18.5, which was consistent with previous reports in LPS-induced MIA models [ 7 , 38 ]. However, we found that VAC exerted no obvious effects on the increases in apoptotic cells and proliferative cells in MIA fetal neocortex (Additional file 2 : Figure S1H and I), implying that apoptosis and proliferation may not contribute to the effects of VAC in this study.…”

Section: Resultssupporting

confidence: 93%

Prenatal influenza vaccination rescues impairments of social behavior and lamination in a mouse model of autism

Song

et al. 2018

J Neuroinflammation

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BackgroundPrenatal infection is a substantial risk factor for neurodevelopmental disorders such as autism in offspring. We have previously reported that influenza vaccination (VAC) during early pregnancy contributes to neurogenesis and behavioral function in offspring.ResultsHere, we probe the efficacy of VAC pretreatment on autism-like behaviors in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) mouse model. We show that VAC improves abnormal fetal brain cytoarchitecture and lamination, an effect associated with promotion of intermediate progenitor cell differentiation in MIA fetal brain. These beneficial effects are sufficient to prevent social deficits in adult MIA offspring. Furthermore, whole-genome analysis suggests a strong interaction between Ikzf1 (IKAROS family zinc-finger 1) and neuronal differentiation. Intriguingly, VAC rescues excessive microglial Ikzf1 expression and attenuates microglial inflammatory responses in the MIA fetal brain.ConclusionsOur study implies that a preprocessed influenza vaccination prevents maternal bacterial infection from causing neocortical lamination impairments and autism-related behaviors in offspring.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1252-z) contains supplementary material, which is available to authorized users.

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Section: Resultssupporting

confidence: 93%

Prenatal influenza vaccination rescues impairments of social behavior and lamination in a mouse model of autism

Song

et al. 2018

J Neuroinflammation

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“…It has also been shown that PGN produced by symbiotic microbiota may ‘leak’ into the bloodstream and reach organs distant to the gut, such as the bones (Clarke et al, 2010). Finally, recent findings show that bacterial cell wall peptidoglycan traverses the murine placenta and reach the developing fetal brain where it triggers a TLR2-dependent fetal neuroproliferative response (Humann et al, 2016). A future challenge will be to test whether an NF-κB-dependent response to PGN is also taking place in mammalian neurons and directly influences the animal behavior.…”

Section: Discussionmentioning

confidence: 99%

Peptidoglycan sensing by octopaminergic neurons modulates Drosophila oviposition

Kurz

Charroux

Chaduli

et al. 2017

eLife

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As infectious diseases pose a threat to host integrity, eukaryotes have evolved mechanisms to eliminate pathogens. In addition to develop strategies reducing infection, animals can engage in behaviors that lower the impact of the infection. The molecular mechanisms by which microbes impact host behavior are not well understood. We demonstrate that bacterial infection of Drosophila females reduces oviposition and that peptidoglycan, the component that activates Drosophila antibacterial response, is also the elicitor of this behavioral change. We show that peptidoglycan regulates egg-laying rate by activating NF-κB signaling pathway in octopaminergic neurons and that, a dedicated peptidoglycan degrading enzyme acts in these neurons to buffer this behavioral response. This study shows that a unique ligand and signaling cascade are used in immune cells to mount an immune response and in neurons to control fly behavior following infection. This may represent a case of behavioral immunity.DOI: http://dx.doi.org/10.7554/eLife.21937.001

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“…Dahlgren and colleagues demonstrated that transplacental passage of I 125 -labeled IL-6 was considerably higher at mid-gestation [embryonic day (E) 11-13] as compared to late gestation/near term (E17- 19), suggesting that a less mature placenta may be more permeable to maternal cytokines (101). TLR ligands for specific pathogens were also recently shown to cross the mouse placenta at mid-gestation (E15) and directly impinge upon fetal cells; however, a direct effect on fetal immune cells was not described (104). Whether other TLR ligands can cross the placenta and directly elicit a fetal immune response has not been determined.…”

Section: Unknown Mechanisms Of Fetal Immune Training By Maternal Inflmentioning

confidence: 99%

Training the Fetal Immune System Through Maternal Inflammation—A Layered Hygiene Hypothesis

2020

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Over the last century, the alarming surge in allergy and autoimmune disease has led to the hypothesis that decreasing exposure to microbes, which has accompanied industrialization and modern life in the Western world, has fundamentally altered the immune response. In its current iteration, the "hygiene hypothesis" suggests that reduced microbial exposures during early life restricts the production and differentiation of immune cells suited for immune regulation. Although it is now well-appreciated that the increase in hypersensitivity disorders represents a "perfect storm" of many contributing factors, we argue here that two important considerations have rarely been explored. First, the window of microbial exposure that impacts immune development is not limited to early childhood, but likely extends into the womb. Second, restricted microbial interactions by an expectant mother will bias the fetal immune system toward hypersensitivity. Here, we extend this discussion to hypothesize that the cell types sensing microbial exposures include fetal hematopoietic stem cells, which drive long-lasting changes to immunity.

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Bacterial Peptidoglycan Traverses the Placenta to Induce Fetal Neuroproliferation and Aberrant Postnatal Behavior

Cited by 32 publications

References 0 publications

Prenatal influenza vaccination rescues impairments of social behavior and lamination in a mouse model of autism

Prenatal influenza vaccination rescues impairments of social behavior and lamination in a mouse model of autism

Peptidoglycan sensing by octopaminergic neurons modulates Drosophila oviposition

Training the Fetal Immune System Through Maternal Inflammation—A Layered Hygiene Hypothesis

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