Immunological memory diversity in the human upper airway

The upper airway is an important site of infection, but immune memory in the human upper airway is poorly understood, with implications for COVID-19 and many other human diseases1-4. Here we demonstrate that nasal and nasopharyngeal swabs can be used to obtain insights into these challenging problem...

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Bibliographic Details
Published in:Nature (London) 2024-08, Vol.632 (8025), p.630-636
Main Authors: Ramirez, Sydney I., Faraji, Farhoud, Hills, L. Benjamin, Lopez, Paul G., Goodwin, Benjamin, Stacey, Hannah D., Sutton, Henry J., Hastie, Kathryn M., Saphire, Erica Ollmann, Kim, Hyun Jik, Mashoof, Sara, Yan, Carol H., DeConde, Adam S., Levi, Gina, Crotty, Shane
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Blood & organ donations
CD4 antigen
CD8 antigen
COVID-19
Germinal centers
Immune system
Immunoglobulin A
Immunological memory
Immunology
Infections
Lymphocytes
Lymphocytes B
Lymphocytes T
Memory cells
Mucosal immunity
Plasma cells
Populations
Respiratory tract diseases
Severe acute respiratory syndrome coronavirus 2
T cell receptors
Viral diseases
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Summary:The upper airway is an important site of infection, but immune memory in the human upper airway is poorly understood, with implications for COVID-19 and many other human diseases1-4. Here we demonstrate that nasal and nasopharyngeal swabs can be used to obtain insights into these challenging problems, and define distinct immune cell populations, including antigen-specific memory B cells and T cells, in two adjacent anatomical sites in the upper airway. Upper airway immune cell populations seemed stable over time in healthy adults undergoing monthly swabs for more than were defined. Unexpectedly, germinal centre cells were identified consistently in 1 year, and prominent tissue resident memory T (TRM) cell and B (BRM) cell populations many nasopharyngeal swabs. In subjects with SARS-CoV-2 breakthrough infections, local virus-specific BRM cells, plasma cells and germinal centre B cells were identified, with evidence of local priming and an enrichment of IgA+ memory B cells in upper airway compartments compared with blood. Local plasma cell populations were identified with transcriptional profiles of longevity. Local virus-specific memory CD4+ Trm cells and CD8+ TRM cells were identified, with diverse additional virusspecific T cells. Age-dependent upper airway immunological shifts were observed. These findings provide new understanding of immune memory at a principal mucosal barrier tissue in humans.
ISSN:0028-0836
1476-4687
1476-4687
DOI:10.1038/s41586-024-07748-8