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

We recently found that 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, using a mouse model, we found that depletion of neutrophils at the time of vaccination in female mice led to aberrant T cell responses in the spleen resulting in increased regulatory T cells (Tregs) that was accompanied by a dysregulated cytokine environment. We found that following vaccination, neutrophils influx into secondary lymphoid organs and increase expression of T cell engaging/inhibiting markers. When we depleted Tregs in neutrophil deficient mice at the time of vaccination, the opsonic activity of the antibodies and the ability of the sera to protect naïve hosts against pneumococcal infection significantly increased compared to controls. Importantly, we examined responses following PCV administration in human female participants and found that PCV altered neutrophil phenotype and that in vitro coculture of 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.