VCAM1/VLA4 interaction mediates Ly6Clow monocyte recruitment to the brain in a TNFR signaling dependent manner during fungal infection

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Sun D, Zhang M, Sun P, Liu G, Strickland AB, et al. (2020) VCAM1/VLA4 interaction mediates Ly6C^low monocyte recruitment to the brain in a TNFR signaling dependent manner during fungal infection. PLOS Pathogens 16(2): e1008361.


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.


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