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Ectopic germinal centers in the nasal turbinates contribute to B cell immunity to intranasal viral infection and vaccination

Gailleton, Romain ; Mathew, Nimitha R ; Reusch, Laura ; Schön, Karin ; Scharf, Lydia ; Strömberg, Anneli ; Cvjetkovic, Andrea ; Aziz, Luaay ; Hellgren, Johan and Tang, Ka-Wei , et al. (2025) In Proceedings of the National Academy of Sciences of the United States of America 122(12). p.1-12
Abstract

The nasal mucosa is the first immunologically active site that respiratory viruses encounter and establishing immunity at the initial point of pathogen contact is essential for preventing viral spread. Influenza A virus (IAV) in humans preferentially replicates in the upper respiratory tract (URT) but mouse models of infection result in lower respiratory tract infection. Here, we optimize IAV inoculation to enhance replication in the nasal turbinate (NT) and study local B cell immunity. We demonstrate that URT-targeted IAV infection stimulates robust local B cell responses, including germinal center (GC) B cell formation in the NT, outside of classical nasal-associated lymphoid tissues. NT GC contributes to local tissue-resident B cell... (More)

The nasal mucosa is the first immunologically active site that respiratory viruses encounter and establishing immunity at the initial point of pathogen contact is essential for preventing viral spread. Influenza A virus (IAV) in humans preferentially replicates in the upper respiratory tract (URT) but mouse models of infection result in lower respiratory tract infection. Here, we optimize IAV inoculation to enhance replication in the nasal turbinate (NT) and study local B cell immunity. We demonstrate that URT-targeted IAV infection stimulates robust local B cell responses, including germinal center (GC) B cell formation in the NT, outside of classical nasal-associated lymphoid tissues. NT GC contributes to local tissue-resident B cell generation and enhances local antibody production. Furthermore, URT-focused immunization also induces significant GC formation in the NT. Finally, we detect steady-state GC in the NT of both mice and healthy humans, suggesting continuous immune surveillance triggered by environmental stimuli. These findings highlight the pivotal role of the NT in local and systemic immunity, with important implications for future mucosal vaccines targeting the upper airways.

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publication status
published
subject
keywords
Germinal Center/immunology, Animals, B-Lymphocytes/immunology, Mice, Humans, Turbinates/immunology, Influenza A virus/immunology, Vaccination, Influenza Vaccines/immunology, Orthomyxoviridae Infections/immunology, Nasal Mucosa/immunology, Female, Administration, Intranasal, Mice, Inbred C57BL, Influenza, Human/immunology, Male
in
Proceedings of the National Academy of Sciences of the United States of America
volume
122
issue
12
article number
e2421724122
pages
1 - 12
publisher
National Academy of Sciences
external identifiers
  • scopus:105001050688
  • pmid:40112112
ISSN
1091-6490
DOI
10.1073/pnas.2421724122
language
English
LU publication?
yes
id
beb474d9-331c-45ea-8115-de1107d73e6b
date added to LUP
2025-03-26 10:14:34
date last changed
2025-07-04 09:58:52
@article{beb474d9-331c-45ea-8115-de1107d73e6b,
  abstract     = {{<p>The nasal mucosa is the first immunologically active site that respiratory viruses encounter and establishing immunity at the initial point of pathogen contact is essential for preventing viral spread. Influenza A virus (IAV) in humans preferentially replicates in the upper respiratory tract (URT) but mouse models of infection result in lower respiratory tract infection. Here, we optimize IAV inoculation to enhance replication in the nasal turbinate (NT) and study local B cell immunity. We demonstrate that URT-targeted IAV infection stimulates robust local B cell responses, including germinal center (GC) B cell formation in the NT, outside of classical nasal-associated lymphoid tissues. NT GC contributes to local tissue-resident B cell generation and enhances local antibody production. Furthermore, URT-focused immunization also induces significant GC formation in the NT. Finally, we detect steady-state GC in the NT of both mice and healthy humans, suggesting continuous immune surveillance triggered by environmental stimuli. These findings highlight the pivotal role of the NT in local and systemic immunity, with important implications for future mucosal vaccines targeting the upper airways.</p>}},
  author       = {{Gailleton, Romain and Mathew, Nimitha R and Reusch, Laura and Schön, Karin and Scharf, Lydia and Strömberg, Anneli and Cvjetkovic, Andrea and Aziz, Luaay and Hellgren, Johan and Tang, Ka-Wei and Bemark, Mats and Angeletti, Davide}},
  issn         = {{1091-6490}},
  keywords     = {{Germinal Center/immunology; Animals; B-Lymphocytes/immunology; Mice; Humans; Turbinates/immunology; Influenza A virus/immunology; Vaccination; Influenza Vaccines/immunology; Orthomyxoviridae Infections/immunology; Nasal Mucosa/immunology; Female; Administration, Intranasal; Mice, Inbred C57BL; Influenza, Human/immunology; Male}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{12}},
  pages        = {{1--12}},
  publisher    = {{National Academy of Sciences}},
  series       = {{Proceedings of the National Academy of Sciences of the United States of America}},
  title        = {{Ectopic germinal centers in the nasal turbinates contribute to B cell immunity to intranasal viral infection and vaccination}},
  url          = {{http://dx.doi.org/10.1073/pnas.2421724122}},
  doi          = {{10.1073/pnas.2421724122}},
  volume       = {{122}},
  year         = {{2025}},
}