Immune Protection against Virus Challenge in Aging Mice Is Not Affected by Latent Herpesviral Infections

Marandu, Thomas F.; Oduro, Jennifer D.; Borkner, Lisa; Dekhtiarenko, Iryna; Uhrlaub, Jennifer L.; Drabig, Anja; Kröger, Andrea; Nikolich‐Žugich, Janko; Čičin-Šain, Luka

doi:10.1128/jvi.01989-15

Cited by 35 publications

(21 citation statements)

References 23 publications

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“…We previously reported that old mice, infected with MCMV for life, and challenged with a novel pathogen (Listeria monocytogenes) in old age, mount primary CD8 T cell responses with modestly reduced effector function and bacterial clearance (12). However, in these, and other similar experiments (19)(20)(21), mortality from third-party infection was not increased by lifelong CMV infection.…”

mentioning

confidence: 74%

Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection

Smithey

Venturi

Davenport

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Lifelong interactions between host and the ubiquitous and persistent cytomegalovirus (CMV) have been proposed to contribute to the age-related decline in immunity. Prior work from us and others found some support for that idea, yet evidence that this led to increased vulnerability to other infections was not obtained. Moreover, evidence has accumulated that CMV infection can be beneficial to immune defense in young/adult mice and humans, dominantly via enhanced innate immunity. Here, we describe an unexpected impact of murine CMV (MCMV) upon the T cell response of old mice to expressing the model antigen, OVA (Lm-OVA). Single-cell sequencing of the OVA-specific CD8 T cell receptor β (TCRβ) repertoire of old mice demonstrated that old MCMV-infected mice recruited many diverse clonotypes that afforded broad and often more efficient recognition of antigenic peptide variants. This stood in contrast to old control mice, which exhibited strong narrowing and homogenization of the elicited repertoire. High-throughput sequencing of the total naïve CD8 TCRβ repertoire showed that many of these diverse OVA-specific clonotypes were present in the naïve CD8 repertoire of mice in all groups (adult, old control, and old MCMV) yet were only recruited into the Lm-OVA response in MCMV old mice. These results have profound implications for our understanding of T cell immunity over a life span and suggest that our coevolution with CMV may include surprising, potentially positive impacts on adaptive heterologous immunity in late life.

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mentioning

confidence: 74%

Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection

Smithey

Venturi

Davenport

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…It is important to emphasize that phenotyping for immune aging will necessarily require concurrent measurements of absolute lymphocyte counts per milliliter of blood. Namely, lowered percentages, but not absolute counts of naïve cells may also be observed due to expansions of TTDE population in persistent herpes viral infections , but this does not impair immune protection against infections . In conclusion, a combination of six markers (CD11a, CD44, CD27, KLRG1, CD62L, and CD122) allows the distinction between TN, TCM/TVM, TEM, and TTDE T cell populations in chronically infected mice (Table ), with a robust identification of age‐related losses of naïve cell populations and increases in terminally differentiated CD8 T cells, matching functional changes in aging humans.…”

Section: Flow Cytometric Phenotyping Of Cells Across Species and Tissuesmentioning

confidence: 88%

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

et al. 2019

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These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer‐reviewed by leading experts in the field, making this an essential research companion.

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“…Latent infection with the γ-herpesvirus used in our studies, MHV68, alters the number and phenotype of memory CD8+ T cells (Barton et al, 2014). Latent MCMV infection also results in profound alteration in the T cell compartment, leading to impaired naïve T cell function (Cicin-Sain et al, 2012), despite no increase in susceptibility to secondary challenge with influenza virus, West Nile virus, or vesicular stomatitis (Marandu et al, 2015). Any or all of these mechanisms could be important contributors to co-infection associated changes in gene expression and altered antibody responses to YFV vaccination.…”

Section: Discussionmentioning

confidence: 99%

Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response

Reese

Kambal

et al. 2016

Cell Host & Microbe

199

186

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Summary Immune responses differ between laboratory mice and humans. Chronic infection with viruses and parasites are common in humans, but are absent in laboratory mice, and thus represent potential contributors to inter-species differences in immunity. To test this, we sequentially infected laboratory mice with herpesviruses, influenza, and an intestinal helminth, and compared their blood immune signatures to mock-infected mice before and after vaccination against Yellow Fever Virus (YFV-17D). Sequential infection altered pre- and post-vaccination gene expression, cytokines, and antibodies in blood. Sequential pathogen exposure induced gene signatures that recapitulated those seen in blood from pet store-raised versus laboratory mice, and adult versus cord blood in humans. Therefore basal and vaccine-induced murine immune responses are altered by infection with agents common outside of barrier facilities. This raises the possibility that we can improve mouse models of vaccination and immunity by selective microbial exposure of laboratory animals to mimic that of humans.

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Immune Protection against Virus Challenge in Aging Mice Is Not Affected by Latent Herpesviral Infections

Cited by 35 publications

References 23 publications

Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection

Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response

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