Innate immune responses to Mycobacterium ulcerans via toll-like receptors and dectin-1 in human keratinocytes.

Publisher: Hindawi Country of Publication: India NLM ID: 100883691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1462-5822 (Electronic) Linking ISSN: 14625814 NLM ISO Abbreviation: Cell Microbiol Subsets: MEDLINE

Publication: 2022- : Mumbai : Hindawi
Original Publication: Oxford : Wiley-Blackwell, c1999-

Host-Pathogen Interactions* ; Immunity, Innate* ; Keratinocytes*/immunology ; Keratinocytes*/metabolism ; Keratinocytes*/microbiology; Membrane Proteins/*metabolism ; Mycobacterium ulcerans/*pathogenicity ; Nerve Tissue Proteins/*metabolism ; Toll-Like Receptor 2/*metabolism ; Toll-Like Receptor 4/*metabolism; Antimicrobial Cationic Peptides/genetics ; Antimicrobial Cationic Peptides/metabolism ; Cell Line ; Cells, Cultured ; Chemokines/genetics ; Chemokines/metabolism ; Epidermal Cells ; Epidermis/immunology ; Epidermis/microbiology ; Gene Expression Regulation/immunology ; Humans ; Lectins, C-Type ; Membrane Proteins/genetics ; Mycobacterium ulcerans/immunology ; Nerve Tissue Proteins/genetics ; Toll-Like Receptor 2/genetics ; Toll-Like Receptor 4/genetics ; Cathelicidins

Mycobacterium ulcerans (MU), an environmental pathogen, causes Buruli ulcer, a severe skin disease. We hypothesized that epidermal keratinocytes might not be a simple barrier, but play a role during MU infection through pattern-recognition receptors expressed in keratinocytes. We found that keratinocyte Toll-like receptors (TLRs) 2 and 4 and Dectin-1 actively participate in the innate immune response to MU, which includes the internalization of bacteria, the production of reactive oxygen species (ROS), and the expression of chemokines and LL-37. Human keratinocytes constitutively expressed TLRs 2 and 4 and induced Dectin-1 in response to MU. Exposing keratinocytes to MU resulted in rapid ROS production, which in turn contributed to the mRNA and protein expression of LL-37. In addition, TLR2, Dectin-1 and, to an extent, TLR4 are essential for the MU-mediated expression of CXCL8, CCL2 and LL-37 in keratinocytes. Furthermore, confocal analysis showed that the Dectin-1 is necessary for keratinocytes to internalize bacilli. Importantly, blockade of ROS and LL-37 significantly increased the intracellular MU growth in keratinocytes, suggesting an important role of these mediators for cutaneous innate immune responses. Our results demonstrate that TLR2, TLR4 and Dectin-1 actively sense, internalize and respond in an innate way to MU in human epidermal keratinocytes.

0 (Antimicrobial Cationic Peptides)
0 (Chemokines)
0 (Lectins, C-Type)
0 (Membrane Proteins)
0 (Nerve Tissue Proteins)
0 (TLR2 protein, human)
0 (Toll-Like Receptor 2)
0 (Toll-Like Receptor 4)
0 (dectin 1)
0 (Cathelicidins)

Date Created: 20090113 Date Completed: 20090518 Latest Revision: 20221207

20240829

10.1111/j.1462-5822.2009.01285.x

19134118