Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

SLAMF7/STAT6 Pathway Inhibit Innate Immune Response in Late-Stage Human Acanthamoeba Keratitis: A Comparative Transcriptome Analysis

Version 1 : Received: 29 December 2022 / Approved: 3 January 2023 / Online: 3 January 2023 (07:33:07 CET)

A peer-reviewed article of this Preprint also exists.

Wei, Z.; Zhang, Y.; Chen, Q.; Xu, X.; Pan, Z.; Jin, Z.-B.; Liang, Q. SLAMF7/STAT6 Pathway Inhibits Innate Immune Response in Late-Stage Human Acanthamoeba Keratitis: A Comparative Transcriptome Analysis. Microorganisms 2023, 11, 365. Wei, Z.; Zhang, Y.; Chen, Q.; Xu, X.; Pan, Z.; Jin, Z.-B.; Liang, Q. SLAMF7/STAT6 Pathway Inhibits Innate Immune Response in Late-Stage Human Acanthamoeba Keratitis: A Comparative Transcriptome Analysis. Microorganisms 2023, 11, 365.

Abstract

Acanthamoeba keratitis (AK) is a blinding corneal infection caused by the protozoan Acanthamoeba. The long-term course of AK suggests the host immunity could not kill Acanthamoeba rapidly. The immune status is still unclear in the late stage of AK. The comparative transcriptome analysis was made based on the bulk RNA sequencing of cornea tissues from AK patients and donors. Differentially expressed genes and enriched signaling pathways were calculated. CIBERSORT algorithm was used for Immune infiltration analysis of cornea tissue between AK and normal controls. A total of 2668 differentially expressed genes, including 1477 upregulated genes and 1191 downregulated genes, were detected. Gene Ontology analysis revealed that the pathways were significantly enriched in leukocyte migration, regulation of T cell activation, the external side of plasma membrane, collagen-containing extracellular matrix, immune receptor activity and cytokine binding. KEGG pathway analysis showed that the pathways were significantly enriched in the cytokine-cytokine receptor interaction, hematopoietic cell lineage and Staphylococcus aureus infection pathway. The immune infiltration profiles varied little between AK and normal controls. Compared with normal tissue, cornea tissue of AK contained a higher proportion of M0 macrophages and CD8 T cells, while resting memory CD4 T cells contributed to a relatively lower portion (P < 0.05). Finally, the expression levels of cell markers and SLAMF7/STAT6 pathway were confirmed by histopathology examinations, RT-qPCR and western blot.

Keywords

Acanthamoeba keratitis; transcriptome analysis; immune status; differentially expressed genes; SLAMF7/STAT6 pathway

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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