Tumor Necrosis Factor Alpha-Induced Recruitment of Inflammatory Mononuclear Cells Leads to Inflammation and Altered Brain Development in Murine Cytomegalovirus-Infected Newborn Mice

Authors

Maria C. Seleme, University of Alabama at Birmingham
Kate Kosmac, University of KentuckyFollow
Stipan Jonjic, University of Rejika, Croatia
William J. Britt, University of Alabama at Birmingham

Abstract

Congenital human cytomegalovirus (HCMV) infection is a significant cause of abnormal neurodevelopment and long-term neurological sequelae in infants and children. Resident cell populations of the developing brain have been suggested to be more susceptible to virus-induced cytopathology, a pathway thought to contribute to the clinical outcomes following intrauterine HCMV infection. However, recent findings in a newborn mouse model of the infection in the developing brain have indicated that elevated levels of proinflammatory mediators leading to mononuclear cell activation and recruitment could underlie the abnormal neurodevelopment. In this study, we demonstrate that treatment with tumor necrosis factor alpha (TNF-α)-neutralizing antibodies decreased the frequency of CD45⁺ Ly6C^hi CD11b⁺ CCR2⁺ activated myeloid mononuclear cells (MMCs) and the levels of proinflammatory cytokines in the blood and the brains of murine CMV-infected mice. This treatment also normalized neurodevelopment in infected mice without significantly impacting the level of virus replication. These results indicate that TNF-α is a major component of the inflammatory response associated with altered neurodevelopment that follows murine CMV infection of the developing brain and that a subset of peripheral blood myeloid mononuclear cells represent a key effector cell population in this model of virus-induced inflammatory disease of the developing brain.

Document Type

Article

Publication Date

4-2017

Notes/Citation Information

Published in Journal of Virology, v. 91, issue 8, e01983-16, p. 1-22.

Copyright © 2017 American Society for Microbiology. All Rights Reserved.

The copyright holder has granted the permission for posting the article here.

Digital Object Identifier (DOI)

https://doi.org/10.1128/JVI.01983-16

Repository Citation

Seleme, Maria C.; Kosmac, Kate; Jonjic, Stipan; and Britt, William J., "Tumor Necrosis Factor Alpha-Induced Recruitment of Inflammatory Mononuclear Cells Leads to Inflammation and Altered Brain Development in Murine Cytomegalovirus-Infected Newborn Mice" (2017). Physical Therapy Faculty Publications. 82.
https://uknowledge.uky.edu/rehabsci_facpub/82