CCL28 modulates neutrophil responses and impacts the trajectory of mucosal infections
CCL28 modulates neutrophil responses and impacts the trajectory of mucosal infections
Summary 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.
Raffatellu Manuela、Silva Steven、Dillon Nicholas、Torres-Ruiz Jiram、Cervantes-Diaz Rodrigo、Perez-Fragoso Alfredo、Maravillas-Montero Jose L.、Gomez-Martin Diana、Nuccio Sean-Paul、Brandt Stephanie L.、Melchior Karine、Lee Michael H.、Sosa-Hernandez Victor A.、Romero-Ramirez Sandra、Gerner Romana R.、Nizet Victor、Perez-Lopez Araceli
Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San Diego||Department of Microbiology and Molecular Genetics, University of California Irvine||Center for Microbiome Innovation, University of California San Diego||Chiba University-UC San Diego Center for Mucosal Immunology, Allergy, and Vaccines (CU-UCSD cMAV)Division of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San DiegoDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San DiegoDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias M¨|dicas y Nutrici¨?n Salvador Zubir¨￠n||Emergency Medicine Department, Instituto Nacional de Ciencias M¨|dicas y Nutrici¨?n Salvador Zubir¨￠nRed de Apoyo a la Investigaci¨?n, Universidad Nacional Aut¨?noma de M¨|xico and Instituto Nacional de Ciencias M¨|dicas y Nutrici¨?n Salvador Zubir¨￠n||Departamento de Biomedicina Molecular, Centro de Investigaci¨?n y de Estudios Avanzados del Instituto Polit¨|cnico NacionalDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias M¨|dicas y Nutrici¨?n Salvador Zubir¨￠nRed de Apoyo a la Investigaci¨?n, Universidad Nacional Aut¨?noma de M¨|xico and Instituto Nacional de Ciencias M¨|dicas y Nutrici¨?n Salvador Zubir¨￠nDepartment of Immunology and Rheumatology, Instituto Nacional de Ciencias M¨|dicas y Nutrici¨?n Salvador Zubir¨￠nDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San Diego||Department of Microbiology and Molecular Genetics, University of California IrvineDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San DiegoDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San DiegoDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San DiegoRed de Apoyo a la Investigaci¨?n, Universidad Nacional Aut¨?noma de M¨|xico and Instituto Nacional de Ciencias M¨|dicas y Nutrici¨?n Salvador Zubir¨￠n||Departamento de Biomedicina Molecular, Centro de Investigaci¨?n y de Estudios Avanzados del Instituto Polit¨|cnico NacionalRed de Apoyo a la Investigaci¨?n, Universidad Nacional Aut¨?noma de M¨|xico and Instituto Nacional de Ciencias M¨|dicas y Nutrici¨?n Salvador Zubir¨￠n||Facultad de Medicina, Universidad Nacional Aut¨?noma de M¨|xicoDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San DiegoDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San Diego||Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego||Center for Microbiome Innovation, University of California San DiegoDivision of Host-Microbe Systems & Therapeutics, Department of Pediatrics, University of California San Diego||Department of Microbiology and Molecular Genetics, University of California Irvine||Biomedicine Research Unit, Facultad de Estudios Superiores Iztacala, Universidad Nacional Aut¨?noma de M¨|xico
基础医学微生物学
Raffatellu Manuela,Silva Steven,Dillon Nicholas,Torres-Ruiz Jiram,Cervantes-Diaz Rodrigo,Perez-Fragoso Alfredo,Maravillas-Montero Jose L.,Gomez-Martin Diana,Nuccio Sean-Paul,Brandt Stephanie L.,Melchior Karine,Lee Michael H.,Sosa-Hernandez Victor A.,Romero-Ramirez Sandra,Gerner Romana R.,Nizet Victor,Perez-Lopez Araceli.CCL28 modulates neutrophil responses and impacts the trajectory of mucosal infections[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.03.19.436197.点此复制
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