Neonatal immune cells have heightened responses following in-utero exposure to chorioamnionitis or COVID-19

Gilley, Annemarie; Boly, Timothy J.; Paden, Austin; Bermick, Jennifer

doi:10.1038/s41390-023-02888-5

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…The levels of cytokines and chemokines in mouse serum and lung homogenates were determined using the Bio-Plex Multiplex Immunoassay System as described previously (Bioplex 200 machine, Biorad, Hercules, CA, USA) (71). Repeat freeze-thaw cycles were avoided to minimize protein degradation.…”

Section: Methodsmentioning

confidence: 99%

A predominately pulmonary activation of complement in a mouse model of severe COVID-19

Szachowicz,

Wohlford-Lenane,

Heinen

et al. 2024

Preprint

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Evidence from in vitro studies and observational human disease data suggest the complement system plays a significant role in SARS-CoV-2 pathogenesis, although how complement dysregulation develops in patients with severe COVID-19 is unknown. Here, using a mouse-adapted SARS-CoV-2 virus (SARS2-N501YMA30) and a mouse model of severe COVID-19, we identify significant serologic and pulmonary complement activation following infection. We observed C3 activation in airway and alveolar epithelia, and in pulmonary vascular endothelia. Our evidence suggests that while the alternative pathway is the primary route of complement activation, components of both the alternative and classical pathways are produced locally by respiratory epithelial cells following infection, and increased in primary cultures of human airway epithelia in response to cytokine exposure. This locally generated complement response appears to precede and subsequently drive lung injury and inflammation. Results from this mouse model recapitulate findings in humans, which suggest sex-specific variance in complement activation, with predilection for increased C3 activity in males, a finding that may correlate with more severe disease. Our findings indicate that complement activation is a defining feature of severe COVID-19 in mice and lay the foundation for further investigation into the role of complement in COVID-19.

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Section: Methodsmentioning

confidence: 99%

A predominately pulmonary activation of complement in a mouse model of severe COVID-19

Szachowicz,

Wohlford-Lenane,

Heinen

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

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The fetal programming effect of maternal immune activation (MIA) on the offspring’s immune system

Hofsink,

Groenink,

Plösch

2024

Semin Immunopathol

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The first 1000 days of life is a critical period of development in which adverse circumstances can have long-term consequences for the child’s health. Maternal immune activation is associated with increased risk of neurodevelopmental disorders in the child. Aberrant immune responses have been reported in individuals with neurodevelopmental disorders. Moreover, lasting effects of maternal immune activation on the offspring’s immune system have been reported. Taken together, this indicates that the effect of maternal immune activation is not limited to the central nervous system. Here, we explore the impact of maternal immune activation on the immune system of the offspring. We first describe the development of the immune system and provide an overview of reported alterations in the cytokine profiles, immune cell profiles, immune cell function, and immune induction in pre-clinical models. Additionally, we highlight recent research on the impact of maternal COVID-19 exposure on the neonatal immune system and the potential health consequences for the child. Our review shows that maternal immune activation alters the offspring’s immune system under certain conditions, but the reported effects are conflicting and inconsistent. In general, epigenetic modifications are considered the mechanism for fetal programming. The available data was insufficient to identify specific pathways that may contribute to immune programming. As a consequence of the COVID-19 pandemic, more research now focuses on the possible health effects of maternal immune activation on the offspring. Future research addressing the offspring’s immune response to maternal immune activation can elucidate specific pathways that contribute to fetal immune programming and the long-term health effects for the offspring.

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Association of antenatal or neonatal SARS-COV-2 exposure with developmental and respiratory outcomes, and healthcare usage in early childhood: a national prospective cohort study

Jackson,

Cornish,

Daskalopoulou

et al. 2024

eClinicalMedicine

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Neonatal immune cells have heightened responses following in-utero exposure to chorioamnionitis or COVID-19

Cited by 3 publications

References 39 publications

A predominately pulmonary activation of complement in a mouse model of severe COVID-19

A predominately pulmonary activation of complement in a mouse model of severe COVID-19

The fetal programming effect of maternal immune activation (MIA) on the offspring’s immune system

Association of antenatal or neonatal SARS-COV-2 exposure with developmental and respiratory outcomes, and healthcare usage in early childhood: a national prospective cohort study

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