RGD Reference Report - Inhibition of TREM-1 and Dectin-1 Alleviates the Severity of Fungal Keratitis by Modulating Innate Immune Responses. - Rat Genome Database

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Inhibition of TREM-1 and Dectin-1 Alleviates the Severity of Fungal Keratitis by Modulating Innate Immune Responses.

Authors: Zhong, J  Huang, W  Deng, Q  Wu, M  Jiang, H  Lin, X  Sun, Y  Huang, X  Yuan, J 
Citation: Zhong J, etal., PLoS One. 2016 Mar 10;11(3):e0150114. doi: 10.1371/journal.pone.0150114. eCollection 2016.
RGD ID: 11526921
Pubmed: (View Article at PubMed) PMID:26963514
DOI: Full-text: DOI:10.1371/journal.pone.0150114

PURPOSE: To explore the possibility that inhibiting triggering receptor expressed on myeloid cells-1 (TREM-1) and Dendritic cell-associated C-type lectin-1(Dectin-1) could modulate the innate immune response and alleviate the severity of corneal fungal keratitis. METHOD: TREM-1 and Dectin-1 expression was detected in fungus-infected human corneal specimens by real-time PCR. C57BL/6 (B6) mice were injected with Aspergillus fumigatus and divided into 4 groups that received subconjunctival injections of PBS and IgG as a control (group I), mTREM-1/IgG fusion protein (group II), the soluble beta-glucan antagonist laminarin (group III), or mTREM-1/Fc and laminarin (group IV). Corneal virulence was evaluated based on clinical scores. TREM-1 and Dectin-1 mRNA levels were assayed using real-time PCR. The distribution patterns of TREM-1, Dectin-1 and cellular infiltrates in fungus-infected corneas were examined by immunohistochemistry. Moreover, changes in T Helper Type1 (Th1)-/ T Helper Type1 (Th2)- type cytokines and proinflammatory cytokines were measured. RESULTS: The expression of TREM-1 and Dectin-1 increased significantly and correlated positively with the progression of fungal keratitis. Most infiltrated cells were neutrophils and secondarily macrophages in infected cornea. The clinical scores decreased after interfering with TREM-1 and Dectin-1 expression in infected mouse corneas. Levels of Th1-type cytokines including interleukin-12 (IL-12), IL-18 and interferon-gamma (IFN-gamma) were decreased in the cornea, while the levels of Th2-type cytokines, including IL-4, IL-5 and IL-10, showed obvious increases. CONCLUSION: TREM-1 and Dectin-1 function concurrently in the corneal innate immune response by regulating inflammatory cytokine expression in fungal keratitis. Inhibition of TREM-1 and Dectin-1 can alleviate the severity of corneal damage by downregulating the excessive inflammatory response.



Disease Annotations    
Fungal Keratitis  (IDA,IEP,IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Clec7a  (C-type lectin domain containing 7A)
Trem1  (triggering receptor expressed on myeloid cells 1)

Genes (Mus musculus)
Clec7a  (C-type lectin domain family 7, member a)
Trem1  (triggering receptor expressed on myeloid cells 1)

Genes (Homo sapiens)
CLEC7A  (C-type lectin domain containing 7A)
TREM1  (triggering receptor expressed on myeloid cells 1)


Additional Information