TY - JOUR
T1 - Keratinocyte infection by Actinomadura madurae triggers an inflammatory response
AU - Santiago-Téllez, Alfonso
AU - Castrillón-Rivera, Laura Estela
AU - Palma-Ramos, Alejandro
AU - Bello-López, Juan Manuel
AU - Sainz-Espuñes, Teresita
AU - Contreras-Paredes, Adriana
AU - Luna-Herrera, Julieta
AU - Castañeda-Sánchez, Jorge Ismael
N1 - Publisher Copyright:
© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Background: Actinomycetoma is a syndrome of the skin characterized by chronic inflammation and lesions with nodular grain-like structures. The most common aetiological agents are Nocardia brasiliensis and Actinomadura madurae. In response to infection with these organisms the body produces an inflammatory immune response in the skin. The aim of the present study was to determine the production of chemokines, pro-inflammatory cytokines, antimicrobial peptides and the expression of Toll-like receptors (TLRs) in keratinocytes infected by A. madurae. Methods: A cell line of HaCaT keratinocytes was infected with A. madurae at a multiplicity of infection of 20:1 for 2 h and the samples were collected from 2 to 72 h post-infection. Intracellular replication of the bacterium was evaluated by counting of colony-forming units, the TLR expression and antimicrobial peptide production were assayed by confocal microscopy and chemokine and pro-inflammatory cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Early in the infection, A. madurae was able to achieve intracellular replication in keratinocytes, however, the cells eventually controlled the infection. In response to the infection, keratinocytes overexpressed TLR2 and TLR6, produced high concentrations of cytokines monocyte chemoattractant protein-1, interleukin 8, human β-defensin-1, human β-defensin-2 and LL37 and low levels of tumour necrosis factor α. Conclusions: The human keratinocytes contribute to the inflammatory process in response to A. madurae infection by overexpressing TLRs and producing chemokines, pro-inflammatory cytokines and antimicrobial peptides.
AB - Background: Actinomycetoma is a syndrome of the skin characterized by chronic inflammation and lesions with nodular grain-like structures. The most common aetiological agents are Nocardia brasiliensis and Actinomadura madurae. In response to infection with these organisms the body produces an inflammatory immune response in the skin. The aim of the present study was to determine the production of chemokines, pro-inflammatory cytokines, antimicrobial peptides and the expression of Toll-like receptors (TLRs) in keratinocytes infected by A. madurae. Methods: A cell line of HaCaT keratinocytes was infected with A. madurae at a multiplicity of infection of 20:1 for 2 h and the samples were collected from 2 to 72 h post-infection. Intracellular replication of the bacterium was evaluated by counting of colony-forming units, the TLR expression and antimicrobial peptide production were assayed by confocal microscopy and chemokine and pro-inflammatory cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Early in the infection, A. madurae was able to achieve intracellular replication in keratinocytes, however, the cells eventually controlled the infection. In response to the infection, keratinocytes overexpressed TLR2 and TLR6, produced high concentrations of cytokines monocyte chemoattractant protein-1, interleukin 8, human β-defensin-1, human β-defensin-2 and LL37 and low levels of tumour necrosis factor α. Conclusions: The human keratinocytes contribute to the inflammatory process in response to A. madurae infection by overexpressing TLRs and producing chemokines, pro-inflammatory cytokines and antimicrobial peptides.
KW - Actinomadura madurae
KW - Actinomycetoma
KW - Inflammation
KW - Innate immunity
KW - Keratinocytes
KW - Mycetoma
KW - Skin
UR - http://www.scopus.com/inward/record.url?scp=85068886186&partnerID=8YFLogxK
U2 - 10.1093/trstmh/trz022
DO - 10.1093/trstmh/trz022
M3 - Artículo
C2 - 30989203
SN - 0035-9203
VL - 113
SP - 392
EP - 398
JO - Transactions of the Royal Society of Tropical Medicine and Hygiene
JF - Transactions of the Royal Society of Tropical Medicine and Hygiene
IS - 7
ER -