Studies in various knockout as well as aged mice have revealed a crucial role for early innate immune responses in protection against CDI, including neutrophil recruitment, generation of nitric oxide through Nos2, and production of IL-22 and its downstream antimicrobial proteins, including calprotectin proteins (S100a8 and S100a9) and lipocalin-2 (Lcn2) (36, 37, 51, –, 54). Here, NOS2 is linked to clostridium difficile infection.