LncSSBP1 Functions as a Negative Regulator of IL-6 Through Interaction With hnRNPK in Bronchial Epithelial Cells Infected With Talaromyces marneffei.

Yinghua Li,Jing Bai,Xiuwan Lan,Guangnan Liu,Huan Chen,Zhiyi He,Shuyi Li,Honglin Luo,Yu Li

doi:10.3389/fimmu.2019.02977

Abstract

Talaromyces marneffei (TM) is an important opportunistic pathogenic fungus capable of causing disseminated lethal infection. In our previous study, we identified host lncRNAs and mRNAs that are dysregulated in TM-infected bronchial epithelial cells. In this report, we verified that IL-6, a key factor in acute inflammatory response, is down-regulated in TM pathogenesis. To elucidate the mechanism of IL-6 regulation, we analyzed the coding/non-coding network, and identified lncSSBP1, a novel lncRNA that is up-regulated by TM. Our results demonstrate that overexpression of lncSSBP1 decreases IL-6 mRNA expression, whereas knockdown of lncSSBP1 enhances IL-6 mRNA expression. Though lncSSBP1 is primarily localized to the nucleus, bioinformatics analysis suggests that it is unlikely to function as competing endogenous RNA or to interact with IL-6 transcription factors. Instead, RNA pull down and RNA immunoprecipitation assays showed that lncSSBP1 binds specifically to heterogenous nuclear ribonucleoprotein K (hnRNPK), which is involved in IL-6 mRNA processing. Our findings suggest that lncSSBP1 may affect IL-6 mRNA expression during TM infection through interaction with hnRNPk in bronchial epithelial cells. Our results suggest a novel pathway by which TM may suppress the immune response to its advantage.

Highlights

Talaromyces marneffei (TM), formerly known as Penicillium marneffei, is a prominent opportunistic pathogen capable of causing disseminated lethal infection
We demonstrate that heterogenous nuclear ribonucleoprotein K serves as a binding partner of both lncSSBP1 and IL-6 mRNA
Like M. tuberculosis, TM is engulfed by monocytes/macrophages and lurks in the reticuloendothelial system [23]

Summary

Introduction

Talaromyces marneffei (TM), formerly known as Penicillium marneffei, is a prominent opportunistic pathogen capable of causing disseminated lethal infection. This thermal dimorphic pathogenic fungus infects immunocompromised hosts including those with acquired immunodeficiency syndrome (AIDS) [1]. In mainland China, the majority of TM infection cases are reported in southern China, and more than 80% of them are from Guangdong and Guangxi Provinces [3]. Current predictions suggest that 16.1% of AIDS patients in Guangxi Province suffer from TM infection, and the mortality rate of TM infection is significantly higher than that of any other AIDS complication [6]. The recurrence rate of disseminated TM is up to 50% [8]

Methods

Results

Conclusion