Langerin is a natural barrier to HIV-1 transmission by Langerhans cells

Nature Medicine 13(3), 367-371 (2007)

Speaker: 黃惠芝                        Place: Room 602

Commentator: 王憲威老師               Date: 2007/5/23 14:00-15:00

Abstract:

HIV-1 infection is a worldwild endemic disease and the major way of infection is through sexual contact. According to previous finding, the host cells were infected with HIV-1 through cis and trans-infection¹. The cis-infection means the viruses entering into host cells demand CD4 and coreceptors, but the trans-infection needs DC-SIGN or other C-type lectin. DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin) which is a specific marker on the dendritic cells surface can bind HIV-1 and assist viruses in transmitting. The Langerhans cells are one of the members of dendritic cells, and they also have a specific C-type lectin marker-Langerin which can bind HIV-1 envelope protein gp120². Therefore the authors want to know what is the role of Langerin in HIV-1 tansmitting. Langerhans cells reside in the epidermis of the skin and in most mucosal epithelia such as foreskin,ectocervix, and vagina. The authors discovered the Langerhans cells decreased the HIV-1_JR- CSF (CCR5-tropic) infection and they used a Langerin blocking antibody-10E2 to confirm theLangerin could diminish the ability of HIV-1 transmitting. Then they created transfected Langerin Raji cells to verify Langerhans cells degraded HIV-1 through Langerin. Furthermore, the authors utilized HIV-1_NL4.3 (CXCR4 tropic single-round pseudotyped HIV-1) and different doses (TCID 10-10,000) to demonstrate that Langerhans cells transmitted HIV-1 required direct infection in high virus load. These data reveals that Langerin is a natural barrier to HIV-1 transmission and may provide a possible strategy to combat HIV-1 infection.

References

1. Wu L, KewalRamani VN Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol. 6(11), 859-868 (2006).

2. Turville, S.G. et al. Diversity of receptors binding HIV on dendritic cell subsets. Nat. Immunol. 3, 975–983 (2002).