IFN-Œ≥ stimulates autophagy-mediated clearance of Burkholderia cenocepacia in human cystic fibrosis macrophages
Authors: Amal O Amer
Benjamin T Kopp
Kaivon Assani
Mia F Tazi
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Burkholderia cenocepacia; cystic fibrosis; autophagy; IFN-Œ≥; macrophages
Affiliations: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America., Department of Microbial Infection and Immunity and the Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America., Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America; Section of Pediatric Pulmonology, Nationwide Children's Hospital, Columbus, Ohio, United States of America.

Abstract:  Burkholderia cenocepacia is a virulent pathogen that causes significant morbidity and mortality in patients with cystic fibrosis (CF), survives intracellularly in macrophages, and uniquely causes systemic infections in CF. Autophagy is a physiologic process that involves engulfing non-functional organelles and proteins and delivering them for lysosomal degradation, but also plays a role in eliminating intracellular pathogens, including B. cenocepacia. Autophagy is defective in CF but can be stimulated in murine CF models leading to increased clearance of B. cenocepacia, but little is known about autophagy stimulation in human CF macrophages. IFN-Œ≥ activates macrophages and increases antigen presentation while also inducing autophagy in macrophages. We therefore, hypothesized that treatment with IFN-Œ≥ would increase autophagy and macrophage activation in patients with CF. Peripheral blood monocyte derived macrophages (MDMs) were obtained from CF and non-CF donors and subsequently infected with B. cenocepacia. Basal serum levels of IFN-Œ≥ were similar between CF and non-CF patients, however after B. cenocepacia infection there is deficient IFN-Œ≥ production in CF MDMs. IFN-Œ≥ treated CF MDMs demonstrate increased co-localization with the autophagy molecule p62, increased autophagosome formation, and increased trafficking to lysosomes compared to untreated CF MDMs. Electron microscopy confirmed IFN-Œ≥ promotes double membrane vacuole formation around bacteria in CF MDMs, while only single membrane vacuoles form in untreated CF cells. Bacterial burden is significantly reduced in autophagy stimulated CF MDMs, comparable to non-CF levels. IL-1Œ≤ production is decreased in CF MDMs after IFN-Œ≥ treatment. Together, these results demonstrate that IFN-Œ≥ promotes autophagy-mediated clearance of B. cenocepacia in human CF macrophages. 

Retracted: No

PubPeer comments:
 Figure 4.  Fluorescence microscopy evaluation of the apoptosis induction in OVCAR-3 cancer cells by rosmarinic acid. The cells were treated with 0 (A), 10 (B), 40 (C) and 160 (D) u00b5M of rosmarinic acid for 48 hrs, stained with Hoechst 33342 and then analyzed by fluorescence microscope at u00d7200 magnification. Increased drug dose led to dose-dependent chromatin condensation and DNA fragmentation .  For comparison: *[left]* Figure 5 from [Zhang, Bao Yang (2019)]https: pubpeer.com publications FCBAA1F7CE3D824E3AFD5107BBD929).  Detection of apoptosis by DAPI staining at indicated doses of genistein . *[right]* Fig 3 from [Duan et al (2019)] .  Figure 3. Mulberroside-A induces dose-dependent apoptotic cell death as indicated by DAPI staining.  , 
 *[right]* Figure 5 from [Zhang et al (2018)] .  Rosmarinic acid treatment led to the suppression of the cancer cell migration in OVCAR-3 cancer cells. The cells were treated with 0, 40 and 160 u00b5M dose of rosmarinic acid for 48 hrs. *[left]* Figure 8 from [Pei et al (2018)] .  Effect of Mahanimbine on the migration of migration of Capan-2 and SW1190 cells, as depicted by wound healing assay . Unexpected overlaps.  , 
 Dear Hoya camphorifolia: Thank you very much for your comments on our paper u201cAnticancer effects of Rosmarinic acid in OVCAR-3 ovarian cancer cells are mediated via induction of apoptosis, suppression of cell migration and modulation of lncRNA MALAT-1 expression Journal of B.U.ON. : official journal of the Balkan Union of Oncology - 2 Comments pubmed: 30003749 issn: 1107-0625 u201d. Your comment has brought our attention. We have carefully checked the original date and noticed that Figure 5 from [Zhang, Bao Yang (2019)] https: pubpeer.com publications FCBAA1F7CE3D824E3AFD5107BBD929).  Detection of apoptosis by DAPI staining at indicated doses of genistein . and Fig 3 from Duan et al (2019).  Figure 3. Mulberroside-A induces dose-dependent apoptotic cell death as indicated by DAPI staining. are strikingly overlapping with the Figure 4 . Figure 8 from Pei et al (2018).  Effect of Mahanimbine on the migration of migration of Capan-2 and SW1190 cells, as depicted by wound healing assay showed unexpected overlaps with Figure 5. Our paper was published in May-Jun 2018, which was prior to these two articles, we are contacting the authors of these two articles to figure out what happened. Thanks again. Best regards Wang tao ,