Frontiers in Immunology (Mar 2023)

C-type lectin receptor agonists elicit functional IL21-expressing Tfh cells and induce primary B cell responses in neonates

  • Maria Vono,
  • Beatris Mastelic-Gavillet,
  • Elodie Mohr,
  • Malin Östensson,
  • Josefine Persson,
  • Thorunn A. Olafsdottir,
  • Sylvain Lemeille,
  • David Pejoski,
  • Oliver Hartley,
  • Dennis Christensen,
  • Peter Andersen,
  • Arnaud M. Didierlaurent,
  • Ali M. Harandi,
  • Ali M. Harandi,
  • Paul-Henri Lambert,
  • Claire-Anne Siegrist

DOI
https://doi.org/10.3389/fimmu.2023.1155200
Journal volume & issue
Vol. 14

Abstract

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IntroductionC-type lectin receptor (CLR) agonists emerged as superior inducers of primary B cell responses in early life compared with Toll-like receptor (TLR) agonists, while both types of adjuvants are potent in adults.MethodsHere, we explored the mechanisms accounting for the differences in neonatal adjuvanticity between a CLR-based (CAF®01) and a TLR4-based (GLA-SE) adjuvant administered with influenza hemagglutinin (HA) in neonatal mice, by using transcriptomics and systems biology analyses.ResultsOn day 7 after immunization, HA/CAF01 increased IL6 and IL21 levels in the draining lymph nodes, while HA/GLA-SE increased IL10. CAF01 induced mixed Th1/Th17 neonatal responses while T cell responses induced by GLA-SE had a more pronounced Th2-profile. Only CAF01 induced T follicular helper (Tfh) cells expressing high levels of IL21 similar to levels induced in adult mice, which is essential for germinal center (GC) formation. Accordingly, only CAF01- induced neonatal Tfh cells activated adoptively transferred hen egg lysozyme (HEL)-specific B cells to form HEL+ GC B cells in neonatal mice upon vaccination with HEL-OVA.DiscussionCollectively, the data show that CLR-based adjuvants are promising neonatal and infant adjuvants due to their ability to harness Tfh responses in early life.

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