Macrophages are dispensable for taste bud regeneration upon nerve injury repair.

Peripheral sensory nerve injury triggers Wallerian degeneration, a process characterized by axonal fragmentation, myelin breakdown, and robust macrophage infiltration. While macrophages are widely implicated in debris clearance and repair within the injured nerve trunk, their functional role in the remodeling of sensory end organs remains poorly defined. Here, we investigated whether macrophages are required for taste bud degeneration and regeneration using a glossopharyngeal nerve transection model in mice. We first observed a marked accumulation of Iba1-positive macrophages in the circumvallate papilla after nerve injury, peaking at 2 weeks and coinciding with maximal taste bud loss. To test the functional requirement for these cells, we used both pharmacological and genetic depletion models. Despite near-complete depletion of infiltrating macrophages, the extent of taste bud loss at 2 weeks was indistinguishable from controls. Likewise, macrophage deficiency did not alter structural recovery at 4 weeks, with taste bud number, size, and the relative composition of different taste cell types remaining unchanged. These findings indicate that the major structural phases of taste bud degeneration and regeneration proceed despite macrophage depletion. Thus, although macrophage infiltration is a prominent feature of peripheral sensory denervation, it is not an essential driver of structural end-organ remodeling in the taste system.