CD44-mediated monocyte transmigration across Cryptococcus neoformans-infected brain microvascular endothelial cells is enhanced by HIV-1 gp41-I90 ectodomain

Background: cryptococcus neoformans (cn) is an important opportunistic pathogen in the immunocompromised people,including aids patients,which leads to fatal cryptococcal meningitis with high mortality rate. previous researches have shown that hiv-1 gp41-i90 ectodomain can enhance cn adhesion to and invasion of brain microvascular endothelial cell (bmec),which constitutes the blood brain barrier (bbb). however,little is known about the role of hiv-1 gp41-i90 in the monocyte transmigration across cn-infected bbb. in the present study,we provide evidence that hiv-1 gp41-i90 and cn synergistically enhance monocytes transmigration across the bbb in vitro and in vivo. the underlying mechanisms for this phenomenon require further study. methods: in this study,the enhancing role of hiv-1 gp41-i90 in monocyte transmigration across cn-infected bbb was demonstrated by performed transmigration assays in vitro and in vivo. results: our results showed that the transmigration rate of monocytes are positively associated with cn and/or hiv-1 gp41-i90,the co-exposure (hiv-1 gp41-i90 + cn) group showed a higher thp-1 transmigration rate (p < 0.01). using cd44 knock-down hbmec or cd44 inhibitor bikunin in the assay,the facilitation of transmigration rates of monocyte enhanced by hiv-1 gp41-i90 was significantly suppressed. western blotting analysis and biotin/avidin enzyme-linked immunosorbent assays (ba-elisas) showed that cn and hiv-1 gp41-i90 could increase the expression of cd44 and icam-1 on the hbmec. moreover,cn and/or hiv-1 gp41-i90 could also induce cd44 redistribution to the membrane lipid rafts. by establishing the mouse cryptococcal meningitis model,we found that hiv-1 gp41-i90 and cn could synergistically enhance the monocytes transmigration,increase the bbb permeability and injury in vivo. conclusions: collectively,our findings suggested that hiv-1 gp41-i90 ectodomain can enhance the transmigration of thp-1 through cn-infected bbb,which may be mediated by cd44. this novel study enlightens the future prospects to elaborate the inflammatory responses induced by hiv-1 gp41-i90 ectodomain and to effectively eliminate the opportunistic infections in aids patients. © 2016 he et al.