title: Candida glabrata induced infection of rat tracheal epithelial cells is mediated by TLR-2 induced activation of NF-κB.
abstract: An increasing number of reports identified Candida glabrata (C. glabrata) as the important causative agent of invasive pulmonary fungal infection. However, little is known about immune responses to C. glabrata in rat tracheal epithelial cell (RTEC). Here, the effect of C. glabrata on RTEC and the role of TLR-2 and NF-κB in the immune response were investigated by treatment with TLR-2 siRNA and NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC), respectively. Our results showed that the knockdown of TLR-2 and pretreatment of PDTC led to inhibition of cell proliferation by C. glabrata, further enhanced cells in G0/G1 phases, and promoted C. glabrata -induced apoptosis. C. glabrata infection induced the expression or secretion of TLR-2, NF-κB, TNF-α, and IL-6, and its effect was inhibited by knockdown of TLR-2. Pretreatment with PDTC inhibited the C. glabrata -induced expression of TLR2, and also inhibited the expression of p65 subunit of NF-κB in the first 4 h. Although the expression of p65 subunit at 6 h was elevated compared to baseline, the C. glabrata -induced expression of TNF-α and IL-6 remained attenuated by PDTC pretreatment. Therefore, C. glabrata recognized the TLR-2 in rat tracheal epithelial cell (RTEC), and then activated the transcription factor NF-κB and further promoted the secretion of TNF-α and IL-6 to contribute to the immune response and inflammation.
authors.affiliation: Department of Intensive Care Unit (ICU), The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Guilin Medical University, Guilin, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Intensive Care Unit (ICU), The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
authors.forename: Cheng-Lin
authors.initials: CL
authors.lastname: Wu
authors.affiliation: The First People's Hospital of Nanning, Nanning, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Intensive Care Unit (ICU), The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Intensive Care Unit (ICU), The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Song
authors.affiliation: Department of Intensive Care Unit (ICU), The Second Affiliated Hospital of Guilin Medical University, Guilin, China. Electronic address: xueping-l@sohu.com.
authors.forename: Xue-Ping
authors.initials: XP
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis; D041221:Candida glabrata / Q000502:physiology*; D002177:Candidiasis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D002453:Cell Cycle; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D054884:Host-Pathogen Interactions; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D014132:Trachea / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha
keywords: Candida glabrata; Invasive pulmonary fungal infection; PAMP; TLR