Cochlin, a glycosylated extracellular matrix protein found in the inner ear, is also expressed in the spleen, but its physiological role there remains unknown. In Immunity, Py et al. show cochlin is secreted by follicular DCs. After bacterial infection, cochlin is proteolytically cleaved by aggrecanase 1 (whose expression is induced by tumor-necrosis factor), which results in the release of a bioactive amino-terminal fragment that functions systemically to activate innate immune responses. Coch−/− mice have normal splenic and lymph node structure and adaptive immunity but fail to control infection with Pseudomonas or Staphylococcus. A defect in the recruitment of monocytes and neutrophils leads to greater bacterial burdens, which ultimately kills the Coch−/− mice. Thus, cleavage of cochlin releases a systemic alarmin that contributes to innate immunity.

Immunity 38, 1063–1072 (2013)