RGD Reference Report - Interactions of thymic stromal lymphopoietin with TLR2 and TLR4 regulate anti-fungal innate immunity in Aspergillus fumigatus-induced corneal infection.

General

Interactions of thymic stromal lymphopoietin with TLR2 and TLR4 regulate anti-fungal innate immunity in Aspergillus fumigatus-induced corneal infection.
Authors:	Dai, Chenyang Wu, Jiayin Chen, Chen Wu, Xinyi
Citation:	Dai C, etal., Exp Eye Res. 2019 May;182:19-29. doi: 10.1016/j.exer.2019.02.020. Epub 2019 Mar 8.
RGD ID:	38549574
Pubmed:	PMID:30853520 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.exer.2019.02.020 (Journal Full-text)
Thymic stromal lymphopoietin (TSLP) is an interleukin 7 (IL-7)-like four helix bundle cytokine that plays diverse roles in the regulation of immune responses. In fungal infection, pattern recognition receptors (PRRs), including the cell surface Toll-like receptors (TLRs) and cytoplasmic NOD-like receptors, recognize pathogen-associated molecular patterns to initiate downstream signal cascades to active immune responses. Our previous studies reported that, in vitro human cornea epithelium cells represented a novel target of TSLP and that TSLP/TSLPR/STAT5 signaling played an important role in the response to Aspergillus fumigatus challenge. TSLP downstream signaling molecules upregulated TLR2 and MyD88/NF kappa B-p65 signaling. This phenomenon suggested that TSLP had an impact on PRRs in antifungal immunity. In mouse fungal keratitis induced by A. fumigatus, TSLP was mainly expressed in the epithelium as well as in some infiltrated immune cells in a time-dependent manner. Exogenous TSLP with Aspergillus led to severe keratitis and worse corneal recovery with higher levels of TLR2, TLR4, IL-6, and IL-8 as well as increased neutrophil infiltration. By contrast, when TSLP was suppressed by siRNA, fungal keratitis was mild with higher levels of antimicrobial peptides such as human beta-defensin (hBD9). Taken together, our data revealed an unreported function of TSLP in mediating an anti-fungal inflammatory response and serving as a target to control tissue injury and infection in A. fumigatus keratitis.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Fungal Keratitis	disease_progression	ISO	Tslp (Mus musculus)	38549574; 38549574		RGD
Fungal Keratitis	disease_progression	IMP		38549574		RGD

Objects Annotated

Genes (Rattus norvegicus)

Tslp (thymic stromal lymphopoietin)

Genes (Mus musculus)

Tslp (thymic stromal lymphopoietin)

Genes (Homo sapiens)

TSLP (thymic stromal lymphopoietin)

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Interactions of thymic stromal lymphopoietin with TLR2 and TLR4 regulate anti-fungal innate immunity in Aspergillus fumigatus-induced corneal infection.