Panicle-Shaped Sympathetic Architecture in the Spleen Parenchyma Modulates Antibacterial Innate Immunity

The nervous system can modulate the body's immunity. However, how efferent neural signals reach out to control the local immunity remains incompletely understood. Here, we report the ImmuView procedure for whole-tissue 3D assessment of neural innervations in the intact immune organs of adult mice. This advanced imaging technique revealed an intricate, panicle-shaped sympathetic architecture in the parenchyma of the spleen but not other immune organs, including the lymph nodes, Peyer's patch, and thymus. In contrast, we observed the minimal presence of parasympathetic innervations in the parenchyma of all of the classic immune organs examined. Specific deletion of the TrkA receptor abolishes the sympathetic architecture in the spleen and such genetic ablation significantly enhanced the spleen antibacterial innate immunity. Moreover, the sympathetic neurotransmitter norepinephrine could inhibit the LPS-elicited innate immunity cell-intrinsically via β2-adrenergic receptor signaling. This study exemplifies the key link that specifically connects the efferent sympathetic signal with the spleen innate immunity.