Sympathetic neurons control adaptive immunity in response to Streptococcus pneumoniae infection by regulating T cell and B cell effector function

This study investigated how lung-innervating sympathetic neurons regulate adaptive immunity. We demonstrate that the nucleus tractus solitarius is activated following Streptococcus pneumoniae pre-exposure and infection, and rostral ventral lateral medulla project sympathetic neurons to the lungs to evoke norepinephrine release. Lung-specific sympathetic neuron depletion reduced B memory and resident memory cells, and antigen-specific IgG. This was phenocopied in Adrb1-/-Adrb2-/- mice (lack β-adrenergic receptors). When B cells from Adrb1-/-Adrb2-/- mice were adoptively transferred into Ighm-/- mice, the bacterial burden was higher than in Ighm-/- mice that received wild-type B cells. Depletion of T cells in Ighm-/- mice that received Adrb1-/- Adrb2-/- B cells had a further increase in bacterial burden compared to adoptively transferred Ighm-/- + Adrb1-/- Adrb2-/- B cells with intact T cells; interferon-γ release was suppressed with T cell depletion. Sensory neurons stimulate sympathetic brainstem centers to evoke norepinephrine release which stimulate T cells to release interferon-γ, and norepinephrine + interferon-γ co-stimulate B cells to increase antigen-specific IgG production coordinating an adaptive immune response to reduce S. pneumoniae infection.