CCL28 modulates neutrophil responses and impacts the trajectory of mucosal infections

Abstract

SummaryThe mucosal chemokine CCL28 is highly upregulated during infection but its role in this context is not well understood. UtilizingCcl28-/-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 againstSalmonella. 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, asCcl28-/-mice were highly susceptible toSalmonellagut infection, but highly resistant to otherwise lethalAcinetobacterlung 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.