Innate immune responses of pulmonary epithelial cells to Burkholderia pseudomallei infection.
BACKGROUND
Burkholderia pseudomallei, a facultative intracellular pathogen, causes systemic infection in humans with high mortality especially when infection occurs through an infectious aerosol. Previous studies indicated that the epithelial cells in the lung are an active participant in host immunity. In this study, we aimed to investigate the innate immune responses of lung epithelial cells against B. pseudomallei.


RESULTS
Using a murine lung epithelial cell line, primary lung epithelial cells and an inhalational murine infection model, we characterized the types of innate immunity proteins and peptides produced upon B. pseudomallei infection. Among a wide panel of immune components studied, increased levels of major pro-inflammatory cytokines IL-6 and TNFalpha, chemokine MCP-1, and up-regulation of secretory leukocyte protease inhibitor (SLPI) and chemokine (C-C motif) ligand 20 (CCL20) were observed. Inhibition assays using specific inhibitors suggested that NF-kappaB and p38 MAPK pathways were responsible for these B. pseudomallei-induced antimicrobial peptides.


CONCLUSIONS
Our findings indicate that the respiratory epithelial cells, which form the majority of the cells lining the epithelial tract and the lung, have important roles in the innate immune response against B. pseudomallei infection.
Sim
Siew Hoon
SH
Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore, Republic of Singapore.
Liu
Yichun
Y
Wang
Dongling
D
Novem
Vidhya
V
Sivalingam
Suppiah Paramalingam
SP
Thong
Tuck Weng
TW
Ooi
Eng Eong
EE
Tan
Gladys
G
D000336:Aerosols; D000818:Animals; D019121:Burkholderia Infections / Q000276:immunology* / Q000378:metabolism; D016957:Burkholderia pseudomallei / Q000378:metabolism*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology*; D005260:Female; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000336:Aerosols; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha