Exogenous remodeling of lung resident macrophages protects against infectious consequences of bone marrow-suppressive chemotherapy.
Infection is the single greatest threat to survival during cancer chemotherapy because of depletion of bone marrow-derived immune cells. Phagocytes, especially neutrophils, are key effectors in immunity to extracellular pathogens, which has limited the development of new approaches to protect patients with cancer and chemotherapy-induced neutropenia. Using a model of vaccine-induced protection against lethal Pseudomonas aeruginosa pneumonia in the setting of chemotherapy-induced neutropenia, we found a population of resident lung macrophages in the immunized lung that mediated protection in the absence of neutrophils, bone marrow-derived monocytes, or antibodies. These vaccine-induced macrophages (ViMs) expanded after immunization, locally proliferated, and were closely related to alveolar macrophages (AMs) by surface phenotype and gene expression profiles. By contrast to AMs, numbers of ViMs were stable through chemotherapy, showed enhanced phagocytic activity, and prolonged survival of neutropenic mice from lethal P. aeruginosa pneumonia upon intratracheal adoptive transfer. Thus, induction of ViMs by tissue macrophage remodeling may become a framework for new strategies to activate immune-mediated reserves against infection in immunocompromised hosts.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105; Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan; peter.murray@stjude.org akinobu.kamei@stjude.org.
Akinobu
A
Kamei
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105.
Geli
G
Gao
Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Geoffrey
G
Neale
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105.
Lip Nam
LN
Loh
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Peter
P
Vogel
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105.
Paul G
PG
Thomas
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105.
Elaine I
EI
Tuomanen
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105 peter.murray@stjude.org akinobu.kamei@stjude.org.
Peter J
PJ
Murray
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers; D001853:Bone Marrow / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000276:immunology*; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology*; D016130:Immunophenotyping; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009503:Neutropenia / Q000209:etiology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control; D054406:Pseudomonas Vaccines / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis
D000970:Antineoplastic Agents; D015415:Biomarkers; D054406:Pseudomonas Vaccines
Pseudomonas aeruginosa pneumonia; chemotherapy; macrophage; neutropenia; vaccine
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