Exaggerated inflammatory responses mediated by Burkholderia cenocepacia in human macrophages derived from Cystic fibrosis patients.
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.
Section of Pediatric Pulmonology, Nationwide Children's Hospital, Columbus, OH, United States. Benjamin.Kopp@NationwideChildrens.org
Benjamin T
BT
Kopp
Basant A
BA
Abdulrahman
Arwa A
AA
Khweek
Surender B
SB
Kumar
Anwari
A
Akhter
Richard
R
Montione
Mia F
MF
Tazi
Kyle
K
Caution
Karen
K
McCoy
Amal O
AO
Amer
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000328:Adult; D017209:Apoptosis; D019121:Burkholderia Infections / Q000382:microbiology*; D057508:Burkholderia cenocepacia; D018932:Chemokine CCL2 / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000382:microbiology / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008247:Lysosomes / Q000382:microbiology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D055815:Young Adult
D000305:Adrenal Cortex Hormones; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D016753:Interleukin-10