The Sympathetic Nervous System Is Necessary for Development of CD4+ T-Cell Memory Following Staphylococcus aureus Infection

Abstract Lymph nodes and spleens are innervated by sympathetic nerve fibers that enter alongside arteries. Despite discovery of these nerve fibers nearly 40 years ago, the role of these nerves during response to infection remains poorly defined. We have found that chemical depletion of sympathetic n...

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Published inThe Journal of infectious diseases Vol. 228; no. 7; pp. 966 - 974
Main Authors Reel, Jessica M, Abbadi, Jumana, Bueno, A Jesse, Cizio, Katarazyna, Pippin, Richard, Doyle, D Annie, Mortan, Laura, Bose, Jeffrey L, Cox, Maureen A
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 03.10.2023
Subjects
Animals
Arteries
CD4 antigen
CD4-Positive T-Lymphocytes
Fibers
Germinal centers
Immunological memory
Lymph Nodes
Lymphocytes T
Major
Mice
Staphylococcal Infections
Staphylococcus aureus
Sympathetic nerves
Sympathetic Nervous System
CD4 T-cell memory
infection
neuroimmunology
immunity
Staphylococcus aureus
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Summary:Abstract Lymph nodes and spleens are innervated by sympathetic nerve fibers that enter alongside arteries. Despite discovery of these nerve fibers nearly 40 years ago, the role of these nerves during response to infection remains poorly defined. We have found that chemical depletion of sympathetic nerve fibers compromises the ability of mice to develop protective immune memory to a Staphylococcus aureus infection. Innate control of the primary infection was not impacted by sympathectomy. Germinal center formation is also compromised in nerve-depleted animals; however, protective antibody responses are still generated. Interestingly, protective CD4+ T-cell memory fails to form in the absence of sympathetic nerves after S aureus infection. Memory CD4+ T cell responses are critical for protection from S. aureus, and do not form in the absence of sympathetic nerves. This may partially explain why patients with peripheral nerve damage are susceptible to recurrent S. aureus infections.
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Potential conflicts of interest. The authors: No reported conflicts of interest.
Presented in part: GRC Lymphatics, Renaissance Il Ciocco, Tuscany, Italy, 30 October–4 November 2022, Poster 17.
J. M. R., J. A., and A. J. B. contributed equally to this work.
All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiad154