Cryptococcus neoformans induces IL-8 secretion and CXCL1 expression by human bronchial epithelial cells.
BACKGROUND
Cryptococcus neoformans (C. neoformans) is a globally distributed fungal pathogen with the potential to cause serious disease, particularly among immune compromised hosts. Exposure to this organism is believed to occur by inhalation and may result in pneumonia and/or disseminated infection of the brain as well as other organs. Little is known about the role of airway epithelial cells in cryptococcal recognition or their ability to induce an inflammatory response.


METHODS
Immortalized BEAS-2B bronchial epithelial cells and primary normal human bronchial epithelium (NHBE) were stimulated in vitro with encapsulated or acapsular C. neoformans cultivated at room temperature or 37 degrees C. Activation of bronchial epithelial cells was characterized by analysis of inflammatory cytokine and chemokine expression, transcription factor activation, fungal-host cell association, and host cell damage.


RESULTS
Viable C. neoformans is a strong activator of BEAS-2B cells, resulting in the production of the neutrophil chemokine Interleukin (IL)-8 in a time- and dose-dependent manner. IL-8 production was observed only in response to acapsular C. neoformans that was grown at 37 degrees C. C. neoformans was also able to induce the expression of the chemokine CXCL1 and the transcription factor CAAT/enhancer-binding protein beta (CEBP/beta) in BEAS-2B cells. NHBE was highly responsive to stimulation with C. neoformans; in addition to transcriptional up regulation of CXCL1, these primary cells exhibited the greatest IL-8 secretion and cell damage in response to stimulation with an acapsular strain of C. neoformans.


CONCLUSIONS
This study demonstrates that human bronchial epithelial cells mediate an acute inflammatory response to C. neoformans and are susceptible to damage by this fungal pathogen. The presence of capsular polysaccharide and in vitro fungal culture conditions modulate the host inflammatory response to C. neoformans. Human bronchial epithelial cells are likely to contribute to the initial stages of pulmonary host defense in vivo.
Guillot
Loïc
L
McGill Centre for the Study of Host Resistance, Room L11-403, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada. loic.guillot@mail.mcgill.ca
Carroll
Scott F
SF
Badawy
Mohamed
M
Qureshi
Salman T
ST
D001980:Bronchi / Q000166:cytology / Q000382:microbiology*; D001991:Bronchitis / Q000382:microbiology* / Q000503:physiopathology; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000378:metabolism*; D003455:Cryptococcus neoformans / Q000472:pathogenicity*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D016209:Interleukin-8 / Q000378:metabolism*; D011336:Probability; D011485:Protein Binding; D012313:RNA / Q000032:analysis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D054360:Chemokine CXCL1; D018836:Inflammation Mediators; D016209:Interleukin-8; D012313:RNA