Human keratinocyte cultures (HaCaT) can be infected by DENV, triggering innate immune responses that include IFNλ and LL37

Lopez-Gonzalez, Moises; Meza-Sánchez, David Eduardo; García‐Cordero, Julio; Bustos-Arriaga, José; Valle, Cristina Vélez-Del; Marsch-Moreno, Meytha; Castro-Jiménez, Tannya; Flores‐Romo, Leopoldo; Santos‐Argumedo, Leopoldo; Gutiérrez-Castañeda, Benito; Cedillo‐Barrón, Leticia

doi:10.1016/j.imbio.2018.07.006

Cited by 23 publications

(22 citation statements)

References 45 publications

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“…The limitation of this experiment was that LL-37 knockdown was not performed on HaCaT cells. The main reason was the low expression of endogenous LL-37 in HaCaT cells, which has been supported by other studies (Svensson et al, 2016 ; Jiang et al, 2018 ; López-González et al, 2018 ; Suhng et al, 2018 ). In addition, cells that were transfected with LL-37 plasmids could not suppress the expression by knockdown.…”

Section: Discussionsupporting

confidence: 65%

LL-37-Induced Autophagy Contributed to the Elimination of Live Porphyromonas gingivalis Internalized in Keratinocytes

Yang

Niu

Pan

et al. 2020

Front. Cell. Infect. Microbiol.

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Porphyromonas gingivalis (P. gingivalis), one of the most important pathogens of periodontitis, is closely associated with the aggravation and recurrence of periodontitis and systemic diseases. Antibacterial peptide LL-37, transcribed from the cathelicidin antimicrobial peptide (CAMP) gene, exhibits a broad spectrum of antibacterial activity and regulates the immune system. In this study, we demonstrated that LL-37 reduced the number of live P. gingivalis (ATCC 33277) in HaCaT cells in a dose-dependent manner via an antibiotic-protection assay. LL-37 promoted autophagy of HaCaT cells internalized with P. gingivalis. Inhibition of autophagy with 3-methyladenine (3-MA) weakened the inhibitory effect of LL-37 on the number of intracellular P. gingivalis. A cluster of orthologous groups (COGs) and a gene ontology (GO) functional analysis were used to individually assign 65 (10%) differentially expressed genes (DEGs) to an "Intracellular trafficking, secretion, and vesicular transport" cluster and 306 (47.08%) DEGs to metabolic processes including autophagy. Autophagy-related genes, a tripartite motif-containing 22 (TRIM22), and lysosomal-associated membrane protein 3 (LAMP3) were identified as potentially involved in LL-37-induced autophagy. Finally, bioinformatics software was utilized to construct and predict the protein-protein interaction (PPI) network of CAMP-TRIM22/LAMP3-Autophagy. The findings indicated that LL-37 can reduce the quantity of live P. gingivalis internalized in HaCaT cells by promoting autophagy in these cells. The transcriptome sequencing and analysis also revealed the potential molecular pathway of LL-37-induced autophagy.

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Section: Discussionsupporting

confidence: 65%

LL-37-Induced Autophagy Contributed to the Elimination of Live Porphyromonas gingivalis Internalized in Keratinocytes

Yang

Niu

Pan

et al. 2020

Front. Cell. Infect. Microbiol.

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“…This amphipathic α-helical peptide is produced by human keratinocytes during inflammatory disorders like psoriasis, lupus erythematosus and contact dermatitis where its concentration can reach 20 µg/mL (Frohm et al, 1997;Braff et al, 2005;Currie et al, 2013). Its up-regulation has also been described during HSV-2 and DENV infections of human keratinocytes (Ogawa et al, 2013;López-González et al, 2018). Moreover, LL-37 expression in combination with hBD-3 was also increased in epidermal and dermal lesions of patients suffering from Kaposi's sarcoma caused by human herpes virus 8 (HHV-8) in comparison to normal skin of healthy controls (Fathy et al, 2012).…”

Section: Human Cathelicidin Ll-37mentioning

confidence: 99%

Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes

et al. 2020

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Keratinocytes, the main cells of the epidermis, are the first site of replication as well as the first line of defense against many viruses such as arboviruses, enteroviruses, herpes viruses, human papillomaviruses, or vaccinia virus. During viral replication, these cells can sense virus associated molecular patterns leading to the initiation of an innate immune response composed of pro-inflammatory cytokines, chemokines, and antimicrobial peptides. Human keratinocytes produce and secrete at least nine antimicrobial peptides: human cathelicidin LL-37, types 1-4 human β-defensins, S100 peptides such as psoriasin (S100A7), calprotectin (S100A8/9) and koebnerisin (S100A15), and RNase 7. These peptides can exert direct antiviral effects on the viral particle or its replication cycle, and indirect antiviral activity, by modulating the host immune response. The purpose of this review is to summarize current knowledge of antiviral and immunomodulatory properties of human keratinocyte antimicrobial peptides.

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“…DENV-2 infection is initiated after inoculation of the virus into the skin during the feeding process of an infected mosquito. Many cells in the skin have been shown to support DENV-2 replication, from the widely studied DCs to non-hematopoietic cells, such as fibroblasts and keratinocytes (5,7). The ability of immune and non-immune skin cells to respond to infection has granted the skin the role of an immune organ, since immunological processes occur here (23).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, resident skin cells are the first target of infection and actively participate in the immune response and wound healing process (3). Our group and others have demonstrated that keratinocytes (4,5), fibroblasts (6, 7), Langerhans cells (LC) (8), dermal dendritic cells (9), and endothelial cells (10) are permissive to different arboviral infections. Dendritic cells (DCs) are one of the most studied cell types as a primary target for dengue.…”

Section: Introductionmentioning

confidence: 98%

Crosstalk Between Dermal Fibroblasts and Dendritic Cells During Dengue Virus Infection

et al. 2020

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Human keratinocyte cultures (HaCaT) can be infected by DENV, triggering innate immune responses that include IFNλ and LL37

Cited by 23 publications

References 45 publications

LL-37-Induced Autophagy Contributed to the Elimination of Live Porphyromonas gingivalis Internalized in Keratinocytes

LL-37-Induced Autophagy Contributed to the Elimination of Live Porphyromonas gingivalis Internalized in Keratinocytes

Antiviral and Immunomodulatory Properties of Antimicrobial Peptides Produced by Human Keratinocytes

Crosstalk Between Dermal Fibroblasts and Dendritic Cells During Dengue Virus Infection

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