Dual Analysis for Mycobacteria and Propionibacteria in Sarcoidosis BAL
- 3 May 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Journal of Clinical Immunology
- Vol. 32 (5), 1129-1140
- https://doi.org/10.1007/s10875-012-9700-5
Abstract
Purpose Sarcoidosis is a non-caseating granulomatous disease for which a role for infectious antigens continues to strengthen. Recent studies have reported molecular evidence of mycobacteria or propionibacteria. We assessed for immune responses against mycobacterial and propionibacterial antigens in sarcoidosis bronchoalveolar lavage (BAL) using flow cytometry, and localized signals consistent with microbial antigens with sarcoidosis specimens, using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS). Methods BAL cells from 27 sarcoidosis, 14 PPD- controls, and 9 subjects with nontuberculosis mycobacterial (NTM) infections were analyzed for production of IFN-γ after stimulation with mycobacterial ESAT-6 and Propionibacterium acnes proteins. To complement the immunological data, MALDI-IMS was performed to localize ESAT-6 and Propionibacterium acnes signals within sarcoidosis and control specimens. Results CD4+ immunologic analysis for mycobacteria was positive in 17/27 sarcoidosis subjects, compared to 2/14 PPD- subjects, and 5/9 NTM subjects (p = 0.008 and p = 0.71 respectively, Fisher’s exact test). There was no significant difference for recognition of P. acnes, which occurred only in sarcoidosis subjects that also recognized ESAT-6. Similar results were also observed for the CD8+ immunologic analysis. MALDI-IMS localized signals consistent with ESAT-6 only within sites of granulomatous inflammation, whereas P. acnes signals were distributed throughout the specimen. Conclusions MALDI-IMS localizes signals consistent with ESAT-6 to sarcoidosis granulomas, whereas no specific localization of P. acnes signals is detected. Immune responses against both mycobacterial and P. acnes are present within sarcoidosis BAL, but only mycobacterial signals are distinct from disease controls. These immunologic and molecular investigations support further investigation of the microbial community within sarcoidosis granulomas.Keywords
This publication has 39 references indexed in Scilit:
- Tuberculous Granuloma Induction via Interaction of a Bacterial Secreted Protein with Host EpitheliumScience, 2010
- Region of Difference 1 in Nontuberculous Mycobacterium Species Adds a Phylogenetic and Taxonomical CharacterJournal of Bacteriology, 2009
- Cellular Responses to Mycobacterial Antigens Are Present in Bronchoalveolar Lavage Fluid Used in the Diagnosis of SarcoidosisInfection and Immunity, 2009
- Characterization of Propionibacterium acnes isolates from sarcoid and non-sarcoid tissues with special reference to cell invasiveness, serotype, and trigger factor gene polymorphismMicrobial Pathogenesis, 2009
- Evidence for Pore Formation in Host Cell Membranes by ESX-1-Secreted ESAT-6 and Its Role in Mycobacterium marinum Escape from the VacuoleInfection and Immunity, 2008
- Molecular imaging of proteins in tissues by mass spectrometryProceedings of the National Academy of Sciences, 2008
- MultipleMycobacteriumantigens induce interferon-γ production from sarcoidosis peripheral blood mononuclear cellsClinical and Experimental Immunology, 2007
- Dynamic Changes in Pro- and Anti-Inflammatory Cytokine Profiles and Gamma Interferon Receptor Signaling Integrity Correlate with Tuberculosis Disease Activity and Response to Curative TreatmentInfection and Immunity, 2007
- Cellular Recognition of Mycobacterium tuberculosis ESAT-6 and KatG Peptides in Systemic SarcoidosisInfection and Immunity, 2007
- Detection of pre-neoplastic and neoplastic prostate disease by MADI profiling of urineBiochemical and Biophysical Research Communications, 2006