Abstract
Recent studies show a substantial incidence of Pneumocystis jirovecii colonization and infection in patients with chronic inflammatory lung conditions. However, little is known about the impact of Pneumocystis upon the regulation of pulmonary immunity. We demonstrate here that Pneumocystis polarizes macrophages towards an alternatively activated macrophage-like phenotype. Genetically engineered mice that lack the ability to signal through IL-4 and IL-13 were used to show that Pneumocystis alternative macrophage activation is dependent upon signaling through these cytokines. To determine whether Pneumocystis-induced macrophage polarization would impact subsequent immune responses, we infected mice with Pneumocystis and then challenged them with Pseudomonas aeruginosa 14 days later. In co-infected animals, a higher proportion of macrophages in the alveolar and interstitial spaces expressed both classical and alternatively activated markers and produced the regulatory cytokines TGFβ and IL-10, as well as higher arginase levels than in mice infected with P. aeruginosa alone. Our results suggest that Pneumocystis reprograms the overall macrophage repertoire in the lung to that of a more alternatively-activated setpoint, thereby altering subsequent immune responses. These data may help to explain the association between Pneumocystis infection and decline in pulmonary function.
Document Type
Article
Publication Date
2-2017
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.imbio.2016.10.003
Funding Information
Research reported in this publication was supported by the National Heart Lung and Blood Institute of the National Institutes of Health under Award Number R01HL088989 to B.A.G, and by the National Institute of Allergy and Infectious Diseases under Award Number R01AI095307 to D.J.F.
Repository Citation
Deckman, Jessica M.; Kurkjian, Cathryn J.; McGillis, Joseph P.; Cory, Theodore J.; Birket, Susan E.; Schutzman, Linda M.; Murphy, Brian S.; Garvy, Beth A.; and Feola, David J., "Pneumocystis Infection Alters the Activation State of Pulmonary Macrophages" (2017). Microbiology, Immunology, and Molecular Genetics Faculty Publications. 137.
https://uknowledge.uky.edu/microbio_facpub/137
Notes/Citation Information
Published in Immunobiology, v. 222, issue 2, p. 188-197.
© 2016 Elsevier GmbH. All rights reserved.
This manuscript version is made available under the CC‐BY‐NC‐ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/.
The document available for download is the author's post-peer-review final draft of the article.