Neutrophils induce effective antibody responses to the pneumococcal conjugate vaccine by inhibiting regulatory T cells

Tchalla, E. Y. I.; Betadpur, A.; Khalil, A. Y.; Lopez, E.; Bhalla, M.; Chang, M.; Wohlfert, E.; Bou Ghanem, E. N.

doi:10.1101/2025.10.28.685204

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bioRxiv · 10.1101/2025.10.28.685204

Neutrophils induce effective antibody responses to the pneumococcal conjugate vaccine by inhibiting regulatory T cells

Tchalla, E. Y. I.·Betadpur, A.·Khalil, A. Y.·Lopez, E.·Bhalla, M.·Chang, M.·Wohlfert, E.·Bou Ghanem, E. N.

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Abstract

Neutrophils are required for production of protective antibodies in response to the pneumococcal conjugate vaccine (PCV), however, the mechanisms behind that are not known. Here, in exploring mechanisms, we found that depletion of neutrophils at the time of vaccination in female mice led to increased regulatory T cells (Tregs) in the spleen that was accompanied by a dysregulated cytokine environment. Following vaccination, neutrophils homed into secondary lymphoid organs where they increased expression of T cell engaging/inhibiting markers. Depletion of Tregs in neutrophil deficient mice restored antibody function against pneumococcal infection. Importantly, PCV vaccination of human female participants altered neutrophil phenotype and in vitro coculture of donor neutrophils with PBMCs at one week following vaccination resulted in lower percentage and proliferation of FOXP3+ T cells, showing the clinical relevance of this phenotype. This work reveals a new mechanism by which neutrophils ensure protective antibody responses to vaccination by suppressing Tregs.

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Tchalla, E. Y. I., Betadpur, A., Khalil, A. Y., Lopez, E., Bhalla, M., Chang, M., Wohlfert, E., Bou Ghanem, E. N.. 2025-10-30. Neutrophils induce effective antibody responses to the pneumococcal conjugate vaccine by inhibiting regulatory T cells. https://doi.org/10.1101/2025.10.28.685204

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