title: Differential Macrophage Polarization from Pneumocystis in Immunocompetent and Immunosuppressed Hosts: Potential Adjunctive Therapy during Pneumonia.
abstract: We explored differential polarization of macrophages during infection using a rat model ofPneumocystispneumonia. We observed enhanced pulmonary M1 macrophage polarization in immunosuppressed (IS) hosts, but an M2 predominant response in immunocompetent (IC) hosts followingPneumocystis cariniichallenge. Increased inflammation and inducible nitric oxide synthase (iNOS) levels characterized the M1 response. However, macrophage ability to produce nitric oxide was defective. In contrast, the lungs of IC animals revealed a prominent M2 gene signature, and these macrophages effectively elicited an oxidative burst associated with clearance ofPneumocystisIn addition, duringP. cariniiinfection the expression of Dectin-1, a critical receptor for recognition and clearance ofP. carinii, was upregulated in macrophages of IC animals but suppressed in IS animals. In the absence of an appropriate cytokine milieu for M2 differentiation,Pneumocystisinduced an M1 response bothin vitroandin vivoThe M1 response induced byP. cariniiwas plastic in nature and reversible with appropriate cytokine stimuli. Finally, we tested whether macrophage polarization can be modulatedin vivoand used to help manage the pathogenesis ofPneumocystispneumonia by adoptive transfer. Treatment with both M1 and M2 cells significantly improved survival ofP. carinii-infected IS hosts. However, M2 treatment provided the best outcomes with efficient clearance ofP. cariniiand reduced inflammation.
authors.affiliation: Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
authors.forename: Vijayalakshmi
authors.initials: V
authors.lastname: Nandakumar
authors.affiliation: Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
authors.forename: Deanne
authors.initials: D
authors.lastname: Hebrink
authors.affiliation: Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
authors.forename: Paige
authors.initials: P
authors.lastname: Jenson
authors.affiliation: Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
authors.forename: Theodore
authors.initials: T
authors.lastname: Kottom
authors.affiliation: Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA limper.andrew@mayo.edu.|Division of Pulmonary Critical Care and Internal Medicine, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Limper
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016867:Immunocompromised Host; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D009026:Mortality; D011010:Pneumocystis / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000628:therapy; D051381:Rats; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D000099181:Dectin-1
keywords: macrophages; pneumocystis; pneumonia; polarization