The mucosal chemokine CCL28 is highly upregulated during infection but its role in this context is not well understood . Utilizing Ccl28-/- mice, we discovered that CCL28 promotes neutrophil recruitment to the infected mucosa . Neutrophils from these tissues expressed the CCL28 receptor CCR3, and CCR3 stimulation enhanced neutrophil antimicrobial activity against Salmonella . Moreover, bone marrow neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli . The functional consequences of CCL28 deficiency were strikingly different between two infection models, as Ccl28-/- mice were highly susceptible to Salmonella gut infection, but highly resistant to otherwise lethal Acinetobacter lung infection . CCL28 thus plays a critical role in the immune response to mucosal pathogens by regulating neutrophil recruitment and activation, a response whose ultimate consequence ranges from beneficial (control of the pathogen) to exceedingly negative (death of the host), depending on the infectious agent and impacted organs.