Exaggerated Inflammatory Responses Mediated by Burkholderia Cenocepacia in Human Macrophages Derived from Cystic Fibrosis Patients
Overview
Authors
Affiliations
Cystic fibrosis (CF) is accompanied with heightened inflammation worsened by drug resistant Burkholderia cenocepacia. Human CF macrophage responses to B. cenocepacia are poorly characterized and variable in the literature. Therefore, we examined human macrophage responses to the epidemic B. cenocepacia J2315 strain in order to identify novel anti-inflammatory targets. Peripheral blood monocyte derived macrophages were obtained from 23 CF and 27 non-CF donors. Macrophages were infected with B. cenocepacia J2315 and analyzed for cytokines, cytotoxicity, and microscopy. CF macrophages demonstrated significant increases in IL-1β, IL-10, MCP-1, and IFN-γ production in comparison to non-CF controls. CF patients on prednisone exhibited globally diminished cytokines compared to controls and other CF patients. CF macrophages also displayed increased bacterial burden and cell death. In conclusion, CF macrophages demonstrate exaggerated IL-1β, IL-10, MCP-1, and IFN-γ production and cell death during B. cenocepacia infection. Treatment with corticosteroids acutely suppressed cytokine responses.
Lipid A Structural Variants Induce Altered Immune Responses.
Hofstaedter C, OKeefe I, Met C, Wu L, Vanderwoude J, Shin S Am J Respir Cell Mol Biol. 2024; 71(2):207-218.
PMID: 38656811 PMC: 11299085. DOI: 10.1165/rcmb.2024-0059OC.
CFTR is required for zinc-mediated antibacterial defense in human macrophages.
Das Gupta K, Curson J, Tarique A, Kapetanovic R, Schembri M, Fantino E Proc Natl Acad Sci U S A. 2024; 121(8):e2315190121.
PMID: 38363865 PMC: 10895263. DOI: 10.1073/pnas.2315190121.
Resident macrophages of the lung and liver: The guardians of our tissues.
Kulle A, Thanabalasuriar A, Cohen T, Szydlowska M Front Immunol. 2022; 13:1029085.
PMID: 36532044 PMC: 9750759. DOI: 10.3389/fimmu.2022.1029085.
The Impact of Highly Effective Modulator Therapy on Cystic Fibrosis Microbiology and Inflammation.
Caverly L, Riquelme S, Hisert K Clin Chest Med. 2022; 43(4):647-665.
PMID: 36344072 PMC: 10224747. DOI: 10.1016/j.ccm.2022.06.007.
Uhl F, Vanherle L, Meissner A Front Immunol. 2022; 13:928300.
PMID: 35967318 PMC: 9365932. DOI: 10.3389/fimmu.2022.928300.