Open AccessVCAM1/VLA4 interaction mediates Ly6Clow monocyte recruitment to the brain in a TNFR signaling dependent manner during fungal infection
Author(s) -
Dong Sun,
Mingshun Zhang,
Peng Sun,
Gongguan Liu,
Ashley B. Strickland,
Yanli Chen,
Yong Fu,
Mohammed Yosri,
Meiqing Shi
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008361
Subject(s) - cryptococcus neoformans , monocyte , biology , immunology , microbiology and biotechnology , signal transduction
Monocytes exist in two major populations, termed Ly6C hi and Ly6C low monocytes. Compared to Ly6C hi monocytes, less is known about Ly6C low monocyte recruitment and mechanisms involved in the recruitment of this subset. Furthermore, the role of Ly6C low monocytes during infections is largely unknown. Here, using intravital microscopy, we demonstrate that Ly6C low 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 Ly6C low monocytes. Furthermore, TNFR signaling is essential for the recruitment through enhancing VLA4 expression on Ly6C low monocytes. Interestingly, the recruited Ly6C low 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 Ly6C low monocytes to the brain and highlights important properties of this subset during infection.