IL-1 receptor regulates S100A8/A9-dependent keratinocyte resistance to bacterial invasion

• Published in: Mucosal immunology Vol. 5; no. 1; pp. 66 - 75
• Main Authors: Sorenson, B S, Khammanivong, A, Guenther, B D, Ross, K F, Herzberg, M C
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-01-2012; Elsevier Limited
• Subjects: Allergology; Antibodies; Biomedical and Life Sciences; Biomedicine; Calgranulin A - genetics; Calgranulin A - immunology; Calgranulin A - metabolism; Calgranulin B - genetics; Calgranulin B - immunology; Calgranulin B - metabolism; Cell Communication; Cell Line; Culture Media, Conditioned - pharmacology; Epithelial Cells - immunology; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Epithelial Cells - pathology; Gastroenterology; Humans; Immunology; Interleukin-1alpha - immunology; Interleukin-1alpha - metabolism; Keratinocytes - immunology; Keratinocytes - metabolism; Keratinocytes - microbiology; Keratinocytes - pathology; Listeria monocytogenes - immunology; Listeria monocytogenes - pathogenicity; Listeriosis - drug therapy; Listeriosis - immunology; Mouth Mucosa - pathology; Receptors, Interleukin-1 - antagonists & inhibitors; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - metabolism; RNA, Small Interfering - genetics; Virulence - drug effects
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2011.48

Previously, we reported that epithelial cells respond to exogenous interleukin (IL)-1α by increasing expression of several genes involved in the host response to microbes, including the antimicrobial protein complex calprotectin (S100A8/A9). Given that S100A8/A9 protects epithelial cells against invading bacteria, we studied whether IL-1α augments S100A8/A9-dependent resistance to bacterial invasion of oral keratinocytes. When inoculated with
Listeria monocytogenes
, human buccal epithelial (TR146) cells expressed and released IL-1α. Subsequently, IL-1α-containing media from
Listeria
-infected cells increased
S100A8
/
A9
gene expression in naïve TR146 cells an IL-1 receptor (IL-1R)-dependent manner. Incubation with exogenous IL-1α decreased
Listeria
invasion into TR146 cells, whereas invasion increased with IL-1R antagonist. Conversely, when
S100A8
/
A9
genes were knocked down using short hairpin RNA (shRNA), TR146 cells responded to exogenous IL-1α with increased intracellular bacteria. These data strongly suggest that infected epithelial cells release IL-1α to signal neighboring keratinocytes in a paracrine manner, promoting S100A8/A9-dependent resistance to invasive
L. monocytogenes
.