Pneumocystis infection alters the activation state of pulmonary macrophages

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• 作者：Jessica M. Deckman^a ; Cathryn J. Kurkjian^a ; Joseph P. McGillis^a ; Theodore J. Cory^b ; Susan E. Birket^b ; Linda M. Schutzman^c ; Brian S. Murphy^c ; Beth A. Garvy^a ; David J. Feola^b ; ^{djfeol2@email.uky.edu}
• 关键词：COPD ; chronic obstructive pulmonary disease ; CF ; cystic fibrosis ; CAM ; classically activated macrophage ; AAM ; alternatively activated macrophage ; BAL ; bronchoalveolar lavage ; MR ; mannose receptor ; CFU ; colony forming unit ; TSB ; trypticase soy broth ; EDTA ; ethylenediaminetetraacetic acid ; MOI ; multiplicity of infection ; FBS ; fetal bovine serum ; ANOVA ; analysis of variance
• 刊名：Immunobiology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：222
• 期：2
• 页码：188-197
• 全文大小：1445 K
• 卷排序：222

文摘

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.