Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States; Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, United States; Biomedicine Research Unit, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla, Mexico
Steven Silva
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States
Michael H Lee
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States
Elisabet Bjånes
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States
Nicholas Dillon
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States; Department of Biological Sciences, University of Texas at Dallas, Richardson, United States
Stephanie L Brandt
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States
Romana R Gerner
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States; School of Life Sciences, ZIEL - Institute for Food and Health, Freising-Weihenstephan, Technical University of Munich, Munich, Germany
Karine Melchior
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States; School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil
Grant J Norton
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States
Felix A Argueta
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States
Frenchesca Dela Pena
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States
Lauren Park
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States
Victor A Sosa-Hernandez
Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico; Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico
Rodrigo Cervantes-Diaz
Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico; Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico
Sandra Romero-Ramirez
Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico; Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
Monica Cartelle Gestal
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, United States
Jose L Maravillas-Montero
Red de Apoyo a la Investigación, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States; Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, United States
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, United States; Center for Microbiome Innovation, University of California San Diego, La Jolla, United States
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California, San Diego, La Jolla, United States; Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, United States; Center for Microbiome Innovation, University of California San Diego, La Jolla, United States; Chiba University-UC San Diego Center for Mucosal Immunology, Allergy, and Vaccines (CU-UCSDcMAV), La Jolla, United States
The chemokine CCL28 is highly expressed in mucosal tissues, but its role during infection is not well understood. Here, we show that CCL28 promotes neutrophil accumulation in the gut of mice infected with Salmonella and in the lung of mice infected with Acinetobacter. Neutrophils isolated from the infected mucosa expressed the CCL28 receptors CCR3 and, to a lesser extent, CCR10, on their surface. The functional consequences of CCL28 deficiency varied between the two infections: Ccl28−/− mice were highly susceptible to Salmonella gut infection but highly resistant to otherwise lethal Acinetobacter lung infection. In vitro, unstimulated neutrophils harbored pre-formed intracellular CCR3 that was rapidly mobilized to the cell surface following phagocytosis or inflammatory stimuli. Moreover, CCL28 stimulation enhanced neutrophil antimicrobial activity, production of reactive oxygen species, and formation of extracellular traps, all processes largely dependent on CCR3. Consistent with the different outcomes in the two infection models, neutrophil stimulation with CCL28 boosted the killing of Salmonella but not Acinetobacter. CCL28 thus plays a critical role in the immune response to mucosal pathogens by increasing neutrophil accumulation and activation, which can enhance pathogen clearance but also exacerbate disease depending on the mucosal site and the infectious agent.