Department of Pathology
Hemic and Immune Systems | Immunology of Infectious Disease | Immunopathology
In adult mice the severity of disease from viral infections is determined by the balance between the efficiency of the immune response and the magnitude of viral load. Here, the impact of this dynamic is examined in neonates. Newborns are highly susceptible to infections due to poor innate responses, lower numbers of T cells and Th2-prone immune responses. Eighty-percent of 7-day old mice, immunologically equivalent to human neonates, succumbed to extremely low doses (5 PFU) of the essentially non-lethal lymphocytic choriomeningitis virus (LCMV-Armstrong) given intraperitoneally. This increased lethality was determined to be dependent upon poor early viral control, as well as, T cells and perforin as assessed in knockout mice. By day 3, these neonatal mice had 400-fold higher viral loads as compared to adults receiving a 10,000-fold (5X104 PFU) higher dose of LCMV. The high viral load in combination with the subsequent immunological defect of partial CD8 T cell clonal exhaustion in the periphery led to viral entry and replication in the brain. Within the brain, CD8 T cells were protected from exhaustion, and thus were able to mediate lethal immunopathology. To further delineate the role of early viral control, neonatal mice were infected with Pichinde virus, a less virulent arenavirus, or LCMV was given to pups of LCMV-immune mothers. In both cases, peak viral load was at least 29-fold lower, leading to functional CD8 T cell responses and 100% survival.
Cytotoxic T cells, Neonates, Viral load, Immune response, Immunopathology, Cloning, Viral replication, Kidneys
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Copyright: © 2021 Kenney et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
Kenney LL, Carter EP, Gil A, Selin LK. T cells in the brain enhance neonatal mortality during peripheral LCMV infection. PLoS Pathog. 2021 Jan 5;17(1):e1009066. doi: 10.1371/journal.ppat.1009066. PMID: 33400715; PMCID: PMC7785120. Link to article on publisher's site
Kenney LL, Carter EP, Gil A, Selin LK. (2021). T cells in the brain enhance neonatal mortality during peripheral LCMV infection. Open Access Publications by UMass Chan Authors. https://doi.org/10.1371/journal.ppat.1009066. Retrieved from https://escholarship.umassmed.edu/oapubs/4567
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