College of Agriculture & Natural Resources
Permanent URI for this communityhttp://hdl.handle.net/1903/1598
The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
Browse
3 results
Search Results
Item CXCR2 is essential for cerebral endothelial activation and leukocyte recruitment during neuroinflammation(Springer Nature, 2015-05-21) Wu, Fengjiao; Zhao, Yawei; Jiao, Tian; Shi, Dongyan; Zhu, Xingxing; Zhang, Mingshun; Shi, Meiqing; Zhou, HongChemokines and chemokine receptors cooperate to promote immune cell recruitment to the central nervous system (CNS). In this study, we investigated the roles of CXCR2 and CXCL1 in leukocyte recruitment to the CNS using a murine model of neuroinflammation. Wild-type (WT), CXCL1−/−, and CXCR2−/− mice each received an intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). Esterase staining and intravital microscopy were performed to examine neutrophil recruitment to the brain. To assess endothelial activation in these mice, the expression of adhesion molecules was measured via quantitative real-time polymerase chain reaction (PCR) and Western blotting. To identify the cellular source of functional CXCR2, chimeric mice were generated by transferring bone marrow cells between the WT and CXCR2−/− mice. Expression levels of the chemokines CXCL1, CXCL2, and CXCL5 were significantly increased in the brain following the i.c.v. injection of LPS. CXCR2 or CXCL1 deficiency blocked neutrophil infiltration and leukocyte recruitment in the cerebral microvessels. In the CXCR2−/− and CXCL1−/− mice, the cerebral endothelial expression of adhesion molecules such as P-selectin and VCAM-1 was dramatically reduced. Furthermore, the bone marrow transfer experiments demonstrated that CXCR2 expression on CNS-residing cells is essential for cerebral endothelial activation and leukocyte recruitment. Compared with microglia, cultured astrocytes secreted a much higher level of CXCL1 in vitro. Astrocyte culture conditioned medium significantly increased the expression of VCAM-1 and ICAM-1 in cerebral endothelial cells in a CXCR2-dependent manner. Additionally, CXCR2 messenger RNA (mRNA) expression in cerebral endothelial cells but not in microglia or astrocytes was increased following tumor necrosis factor-α (TNF-α) stimulation. The intravenous injection of the CXCR2 antagonist SB225002 significantly inhibited endothelial activation and leukocyte recruitment to cerebral microvessels. CXCL1 secreted by astrocytes and endothelial CXCR2 play essential roles in cerebral endothelial activation and subsequent leukocyte recruitment during neuroinflammation.Item VCAM1/VLA4 interaction mediates Ly6Clow monocyte recruitment to the brain in a TNFR signaling dependent manner during fungal infection(PLoS, 2020-02-26) Sun, Donglei; Zhang, Mingshun; Sun, Peng; Liu, Gongguan; Strickland, Ashley B.; Chen, Yanli; Fu, Yong; Yosri, Mohammed; Shi, MeiqingMonocytes 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.Item Fungal dissemination is limited by liver macrophage filtration of the blood(Springer Nature, 2019-10-08) Sun, Donglei; Sun, Peng; Li, Hongmei; Zhang, Mingshun; Liu, Gongguan; Strickland, Ashley B.; Chen, Yanli; Fu, Yong; Xu, Juan; Yosri, Mohammed; Nan, Yuchen; Zhou, Hong; Zhang, Xiquan; Shi, MeiqingFungal dissemination into the bloodstream is a critical step leading to invasive fungal infections. Here, using intravital imaging, we show that Kupffer cells (KCs) in the liver have a prominent function in the capture of circulating Cryptococcus neoformans and Candida albicans, thereby reducing fungal dissemination to target organs. Complement C3 but not C5, and complement receptor CRIg but not CR3, are involved in capture of C. neoformans. Internalization of C. neoformans by KCs is subsequently mediated by multiple receptors, including CR3, CRIg, and scavenger receptors, which work synergistically along with C5aR signaling. Following phagocytosis, the growth of C. neoformans is inhibited by KCs in an IFN-γ independent manner. Thus, the liver filters disseminating fungi from circulation via KCs, providing a mechanistic explanation for the enhanced risk of cryptococcosis among individuals with liver diseases, and suggesting a therapeutic strategy to prevent fungal dissemination through enhancing KC functions.