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ORIGINAL RESEARCH article

Front. Cell. Neurosci.
Sec. Cellular Neurophysiology
Volume 18 - 2024 | doi: 10.3389/fncel.2024.1444876
This article is part of the Research Topic Glial Cells in Health and Disease: Impacts on Neural Circuits and Plasticity View all 5 articles

H7N7 Viral Infection Elicits Pronounced, Sex-Specific Neuroinflammatory Responses in vitro

Provisionally accepted
Lea Gabele Lea Gabele 1,2Isabell Bochow Isabell Bochow 1Nele Rieke Nele Rieke 2Christian Sieben Christian Sieben 2Kristin Michaelsen-Preusse Kristin Michaelsen-Preusse 1Shirin Hosseini Shirin Hosseini 1,2Martin Korte Martin Korte 1,2*
  • 1 Department of Cellular Neurobiology, Zoological Institute, Braunschweig University of Technology, Braunschweig, Germany
  • 2 Helmholtz Center for Infection Research, Helmholtz Association of German Research Centers (HZ), Braunschweig, Germany

The final, formatted version of the article will be published soon.

    Influenza A virus (IAV) infection can increase the risk of neuroinflammation, and subsequent neurodegenerative diseases. Certain IAV strains, such as avian H7N7 subtype, possess neurotropic properties, enabling them to directly invade the brain parenchyma and infect neurons and glia cells. Host sex significantly influences the severity of IAV infections. Studies indicate that females of the reproductive age exhibit stronger innate and adaptive immune responses to IAVs compared to males. This heightened immune response correlates with increased morbidity and mortality, and potential neuronal damage in females. Understanding the sex-specific neurotropism of IAV and associated mechanisms leading to adverse neurological outcomes is essential. Our study reveals that primary hippocampal cultures from female mice show heightened interferon-β and pro-inflammatory chemokine secretion following neurotropic IAV infection. We observed sexspecific differences in microglia activation: both sexes showed a transition into a hyper-ramified state, but only male-derived microglia exhibited an increase in amoeboid-shaped cells. These disparities extended to alterations in neuronal morphology. Neurons from female mice displayed increased spine density within 24 hours post-infection, while no significant change was observed in male cultures. This aligns with sex-specific differences in microglial synaptic pruning. Data suggest that amoeboid-shaped microglia preferentially target postsynaptic terminals, potentially reducing neuronal hyperexcitability. Conversely, hyper-ramified microglia may focus on presynaptic terminals, potentially limiting viral spread. In conclusion, our findings underscore the utility of primary hippocampal cultures, incorporating microglia, as an effective model to study sex-specific, virus-induced effects on brain-resident cells.

    Keywords: Influenza A virus, microglial activation, Sex, Hippocampus, CNS

    Received: 06 Jun 2024; Accepted: 18 Jul 2024.

    Copyright: © 2024 Gabele, Bochow, Rieke, Sieben, Michaelsen-Preusse, Hosseini and Korte. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Martin Korte, Department of Cellular Neurobiology, Zoological Institute, Braunschweig University of Technology, Braunschweig, Germany

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