Tolerance toHaemophilus influenzaeinfection in human epithelial cells: insights from a primary cell-based model

Author:

Kappler UlrikeORCID,Henningham Anna,Nasreen Marufa,Buultjens Andrew H.,Stinear Timothy P.ORCID,Sly Peter,Fantino Emmanuelle

Abstract

AbstractHaemophilus influenzaeis a human respiratory pathogen and inhabits the human respiratory tract as its only niche. Despite this, the molecular mechanisms that allowH. influenzaeto establish persistent infections of human epithelia are not well understood.Here, we have investigated howH. influenzaeadapts to the host environment and triggers the host immune response using a human primary cell-based infection model that closely resembles human nasal epithelia (NHNE).Physiological assays combined with dualRNAseq revealed that NHNE from five healthy donors all responded toH. influenzaeinfection with an initial, ‘unproductive’ inflammatory response that included a strong hypoxia signature but did not produce pro-inflammatory cytokines. Subsequently, an apparent tolerance to large extra- and intracellular burdens ofH. influenzaedeveloped, with NHNE transcriptional profiles resembling the pre-infection state. This occurred in parallel with the development of intracellular bacterial populations, and appears to involve interruption of NFkB signalling. This is the first time that large-scale, persistence-promoting immunomodulatory effects ofH. influenzaeduring infection have been u. Interestingly, NHNE were able to re-activate pro-inflammatory responses towards the end of the 14-day infection resulting in release of pro-inflammatory cytokines (IL8, TNFα). Our data further indicate the presence of infection stage-specific gene expression modules, highlighting fundamental similarities between immune responses in NHNE and canonical immune cells, which merit further investigation.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3