VCAM1/VLA4 Interaction Mediates Ly6Clow Monocyte Recruitment to the Brain in a TNFR Signaling Dependent Manner During Fungal Infection

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2020 Feb 27

PMID 32101593

Citations 21

Authors

Donglei Sun

Mingshun Zhang

Peng Sun

Gongguan Liu

Ashley B Strickland

Yanli Chen

Yong Fu

Mohammed Yosri

Meiqing Shi

Affiliations

Soon will be listed here.

Abstract

Monocytes exist in two major populations, termed Ly6Chi and Ly6Clow monocytes. Compared to Ly6Chi monocytes, less is known about Ly6Clow monocyte recruitment and mechanisms involved in the recruitment of this subset. Furthermore, the role of Ly6Clow monocytes during infections is largely unknown. Here, using intravital microscopy, we demonstrate that Ly6Clow monocytes are predominantly recruited to the brain vasculature following intravenous infection with Cryptococcus neoformans, a fungal pathogen causing meningoencephalitis. The recruitment depends primarily on the interaction of VCAM1 expressed on the brain endothelium with VLA4 expressed on Ly6Clow monocytes. Furthermore, TNFR signaling is essential for the recruitment through enhancing VLA4 expression on Ly6Clow monocytes. Interestingly, the recruited Ly6Clow monocytes internalized C. neoformans and carried the organism while crawling on and adhering to the luminal wall of brain vasculature and migrating to the brain parenchyma. Our study reveals a substantial recruitment of Ly6Clow monocytes to the brain and highlights important properties of this subset during infection.

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