RT Journal Article
SR Electronic
T1 CCL28 modulates neutrophil responses and impacts the trajectory of mucosal infections
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.19.436197
DO 10.1101/2021.03.19.436197
A1 Araceli Perez-Lopez
A1 Steven Silva
A1 Nicholas Dillon
A1 Stephanie L. Brandt
A1 Romana R. Gerner
A1 Michael H. Lee
A1 Karine Melchior
A1 Jiram Torres-Ruiz
A1 Victor A. Sosa-Hernandez
A1 Rodrigo Cervantes-Diaz
A1 Alfredo Perez-Fragoso
A1 Sandra Romero-Ramirez
A1 Diana Gomez-Martin
A1 Jose L. Maravillas-Montero
A1 Sean-Paul Nuccio
A1 Victor Nizet
A1 Manuela Raffatellu
YR 2021
UL http://biorxiv.org/content/early/2021/03/20/2021.03.19.436197.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.