The role of microglia in 67NR mammary tumor‐induced suppression of brain responses to immune challenges in female mice

Author:

Otto‐Dobos L. D.1ORCID,Santos J. C.1,Strehle L. D.1,Grant C. V.1,Simon L. A.1,Oliver B.1,Godbout J. P.123,Sheridan J. F.124,Barrientos R. M.1235,Glasper E. R.12,Pyter L. M.125ORCID

Affiliation:

1. Institute for Behavioral Medicine Research The Ohio State University Columbus Ohio USA

2. Department of Neuroscience The Ohio State University Columbus Ohio USA

3. Chronic Brain Injury Program The Ohio State University Columbus Ohio USA

4. Division of Biosciences College of Dentistry The Ohio State University Columbus Ohio USA

5. Department of Psychiatry and Behavioral Health The Ohio State University Columbus Ohio USA

Abstract

AbstractIt is poorly understood how solid peripheral tumors affect brain neuroimmune responses despite the various brain‐mediated side effects and higher rates of infection reported in cancer patients. We hypothesized that chronic low‐grade peripheral tumor‐induced inflammation conditions microglia to drive suppression of neuroinflammatory responses to a subsequent peripheral immune challenge. Here, Balb/c murine mammary tumors attenuated the microglial inflammatory gene expression responses to lipopolysaccharide (LPS) and live Escherichia coli (E. coli) challenges and the fatigue response to an E. coli infection. In contrast, the inflammatory gene expression in response to LPS or a toll‐like receptor 2 agonist of Percoll‐enriched primary microglia cultures was comparable between tumor‐bearing and ‐free mice, as were the neuroinflammatory and sickness behavioral responses to an intracerebroventricular interleukin (IL)‐1β injection. These data led to the hypothesis that Balb/c mammary tumors blunt the neuroinflammatory responses to an immune challenge via a mechanism involving tumor suppression of the peripheral humoral response. Balb/c mammary tumors modestly attenuated select circulating cytokine responses to LPS and E. coli challenges. Further, a second mammary tumor/mouse strain model (E0771 tumors in C57Bl/6 mice) displayed mildly elevated inflammatory responses to an immune challenge. Taken together, these data indicate that tumor‐induced suppression of neuroinflammation and sickness behaviors may be driven by a blunted microglial phenotype, partly because of an attenuated peripheral signal to the brain, which may contribute to infection responses and behavioral side effects reported in cancer patients. Finally, these neuroimmune effects likely vary based on tumor type and/or host immune phenotype.image

Funder

National Cancer Institute

National Institute of Neurological Disorders and Stroke

Ohio State University

Pelotonia

Publisher

Wiley

Subject

Cellular and Molecular Neuroscience,Biochemistry

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

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