<i>Aspergillus fumigatus</i> promotes T helper type 2 responses through thymic stromal lymphopoietin production by human corneal epithelial cells

Wang, Luping; Wang, Leyi; Wu, Xinyi

doi:10.1111/ceo.12706

Cited by 14 publications

(9 citation statements)

References 45 publications

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“… 13 , 14 , 29 In vitro, Aspergillus fumigatus stimulated the expression of TSLP in cultured human CECs in a TLR2/MyD88 dependent manner. 15 , 16 In this study, we showed that challenging primary HCECs with heat-killed P. aeruginosa resulted in the upregulation of TSLP at mRNA levels within the first 2 hours, and at the protein levels at up to 8 hours. TSLP can also be detected in the culture media at 3 hpi.…”

Section: Discussionmentioning

confidence: 63%

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TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

Cui

Gao

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeWe sought to determine the role of epithelium-produced thymic stromal lymphopoietin (TSLP) and its underlying mechanisms in corneal innate immune defense against Pseudomonas (P.) aeruginosa keratitis.MethodsThe expression of TSLP and TSLPR in cultured human corneal epithelial cells (HCECs) and mouse corneas was determined by PCR, Western, and/or ELISA. Cellular localization of TSLP receptor (TSLPR) was determined by whole mount confocal microscopy. TSLP-TSLPR signaling was downregulated by neutralizing antibodies and/or small interfering (si)RNA; their effects on the severity of P. aeruginosa–keratitis and cytokine expression were assessed using clinical scoring, bacterial counting, PMN infiltration, and real-time PCR. The role of dendritic cells (DCs) in corneal innate immunity was determined by local DC depletion using CD11c-DTR mice.ResultsP. aeruginosa–infection induced the expression of TSLP and TSLPR in both cultured primary HCECs and in C57BL/6 mouse corneas. While TSLP was mostly expressed by epithelial cells, CD11c-positive cells were positive for TSLPR. Targeting TSLP or TSLPR with neutralizing antibodies or TSLPR with siRNA resulted in more severe keratitis, attributable to an increase in bacterial burden and PMN infiltration. TSLPR neutralization significantly suppressed infection-induced TSLP and interleukin (IL)-17C expression and augmented the expression of IL-23 and IL-17A. Local depletion of DCs markedly increased the severity of keratitis and exhibited no effects on TSLP and IL-23 expression while suppressing IL-17A and C expression in P. aeruginosa–infected corneas.ConclusionsThe epithelium-expressed TSLP plays a protective role in P. aeruginosa keratitis through targeting of DCs and in an IL-23/IL-17 signaling pathway-related manner.

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Section: Discussionmentioning

confidence: 63%

“… 13 , 14 and Aspergillus fumigatus keratitis in in vitro cell culture models. 15 , 16 The involvement of TSLP in bacterial keratitis in vivo remains unknown.…”

mentioning

confidence: 99%

TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

Cui

Gao

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…[ 15 ] Both innate and adaptive immunity play an important role in infected corneal tissue at early and late stages of fungal keratitis. The various factors that have been implicated to play a role in host response includes polymorphisms in genes associated Dectin-1/CARD9 and Toll-like receptors (TLRs) pathways,[ 16 ] upregulation of indoleamine 2,3-dioxygenase,[ 17 ] thymic stromal lymphopoietin production by human corneal epithelial cells,[ 18 ] expression of interleukins (IL-8, IL-6 and IL-1β). [ 19 ] A recent study by Karthikeyan et al .…”

Section: Host Immune Response In Fungal Infectionsmentioning

confidence: 99%

Recent advances in diagnosis and management of Mycotic Keratitis

Maharana

Sharma

Nagpal

et al. 2016

Indian J Ophthalmol

100

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Mycotic keratitis is a major cause of corneal blindness, especially in tropical and subtropical countries. The prognosis is markedly worse compared to bacterial keratitis. Delayed diagnosis and scarcity of effective antifungal agents are the major factors for poor outcome. Over the last decade, considerable progress has been made to rapidly diagnose cases with mycotic keratitis and increase the efficacy of treatment. This review article discusses the recent advances in diagnosis and management of mycotic keratitis with a brief discussion on rare and emerging organisms. A MEDLINE search was carried out for articles in English language, with the keywords, mycotic keratitis, fungal keratitis, emerging or atypical fungal pathogens in mycotic keratitis, investigations in mycotic keratitis, polymerase chain reaction in mycotic keratitis, confocal microscopy, treatment of mycotic keratitis, newer therapy for mycotic keratitis. All relevant articles were included in this review. Considering the limited studies available on newer diagnostic and therapeutic modalities in mycotic keratitis, case series as well as case reports were also included if felt important.

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“…In human bronchial epithelium, Af exposure-triggered promotion of Th2 response is associated with inhibition Ribonuclease T2 from Aspergillus fumigatus promotes T helper type 2 responses through M2 polarization of macrophages of interferon-β signaling through the JAK-STAT1 signaling pathway, which shifts epithelial responses from type Th1 to type Th2 (7,8), as well as, activation of protease-activated receptor-2 and tyrosine-protein phosphate nonreceptor type 11, which reduces cXcL10 expression, further favoring induction of a Th2 response (9). In addition, Af has been reported to promote Th2 responses through thymic stromal lymphopoietin production by human corneal epithelial cells (10). Sera from patients with ABPA show increased IgE reactivity to Asp f 2 and Af crude extract; and it has been hypothesized that the Af antigens, Asp f 1 or Asp f 2, may underlie upregulation of Th2 (11).…”

Section: Introductionmentioning

confidence: 99%

Ribonuclease T2 from Aspergillus fumigatus promotes T helper type 2 responses through M2 polarization of macrophages

Chen

Zhong

et al. 2020

Int J Mol Med

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Allergic bronchopulmonary aspergillosis (ABPA) is an allergic immunological response to Aspergillus fumigatus (Af) exposure, which induces a strong T helper 2 (Th2) response via mechanisms that have yet to be elucidated. The aim of the present study was to investigate the hypothesis that T2 ribonuclease from Af (Af RNASET2) induces M2-type macrophage polarization to produce a T helper 2 (Th2) immune response. Recombinant Af RNASET2 (rAf RNASET2) was expressed and purified in a prokaryotic pET system and BALB/c mice were immunized with rAf RNASET2 for in vivo analyses. Expression levels of M2 polarization factors were evaluated in RAW264.7 macrophages treated with rAf RNASET2 in vitro using flow cytometry, reverse transcription-quantitative PCR, and western blot analysis. The results predicted that the mature Af RNASET2 protein (382 amino acids; GenBank no. MN593022) contained two conserved amino acid sequence (cAS) domains, termed cAS-1 and cAS-2, which are also characteristic of the RNASET2 family proteins. The protein expression levels of the Th2-related cytokines interleukin (IL)-4, IL-10, and IL-13 were upregulated in mice immunized with rAf RNASET2. RAW264.7 macrophages treated with rAf RNASET2 showed increased mRNA expression levels of M2 factors [arginase 1, Il-10, and Il-13]; however, there was no difference in cells treated with rAf RNASET2 that had been inactivated with a ribonuclease inhibitor (RNasin). The protein expression levels of IL-10 in macrophage culture supernatant were also increased following stimulation with rAf RNASET2. In addition, rAf RNASET2 upregulated the expression of phosphorylated mitogen activated protein kinases (MAPKs) in RAW264.7 cells, whereas MAPK inhibitors attenuated rAf RNASET2-induced IL-10 expression in RAW264.7 cells. In conclusion, the present study reveals that high rAf RNASET2 activity is required for rAf RNASET2-induced M2 polarization of macrophages and suggests an important immune regulatory role for Af RNASET2 in ABPA pathogenesis.

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Aspergillus fumigatus promotes T helper type 2 responses through thymic stromal lymphopoietin production by human corneal epithelial cells

Abstract: These findings suggested that HCEC-derived TSLP has a key role in adaptive immune responses of fungal keratitis via skewing Th2 differentiation and promoting humoral immunity.

Cited by 14 publications

References 45 publications

TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

Recent advances in diagnosis and management of Mycotic Keratitis

Ribonuclease T2 from Aspergillus fumigatus promotes T helper type 2 responses through M2 polarization of macrophages

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