LANGERIN IS A NATURAL BARRIER TO HIV.

 

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

 

Human immunodeficiency virus-1 (HIV-1) is primarily transmitted sexually.

 

Dendritic cells (DCs) in the subepithelium transmit HIV-1 to T cells through

the C-type lectin DC-specific intercellular adhesion molecule (ICAM)-3- grabbing nonintegrin (DC-SIGN).

However, the epithelial Langerhans cells (LCs) are

the first DC subset to encounter HIV-1.

It has generally been assumed that LCs mediate the transmission of HIV-1

to T cells through the C-type lectin Langerin, similarly to transmission by

DC-SIGN on dendritic cells (DCs).

Here we show that in stark contrast to DC-SIGN, Langerin prevents HIV-1 transmission by LCs.

**********************************************************************************

HIV-1 captured by Langerin was internalized into Birbeck granules and degraded.

[Note: The virus is destroyed by the cells of the inner-foreskin... The argument used by

the proponents of MGM, say the virus enters the body through here. Incorrect!!]

**********************************************************************************

Langerin inhibited LC infection and this mechanism kept LCs refractory

to HIV-1 transmission; inhibition of Langerin allowed LC infection and subsequent HIV-1 transmission.
Notably, LCs also inhibited T-cell infection by viral clearance through Langerin.

Thus Langerin is a natural barrier to HIV-1 infection, and strategies to

combat infection must enhance, preserve or, at the very least, not interfere with Langerin expression and function.

The most common route for HIV-1 infection is through sexual transmission across genital mucosa.

There is a need for microbicides that prevent HIV-1 transmission.

 

1. Progress is hindered because early events in HIV-1 entry remain unclear.

Dendritic cell (DC) subsets in mucosal tissues are thought to transmit HIV-1
to T cells through C-type lectins.

 

2–5. In mucosal tissues, DC subsets can be distinguished by their expression

of C-type lectins 6: Langerhans cells (LCs) specifically express Langerin and DCs express DC-SIGN (Fig. 1a). 

LCs reside in the epidermis of the skin and in most mucosal epithelia,

such as the ectocervix, vagina and foreskin, whereas DC-SIGN + DCs reside
in the subepithelium.

6. Thus, LCs are the first DC subset to encounter HIV-1 (ref. 7)

(Supplementary Fig. 1 online).

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

http://www.circumcisionandhiv.com/files/de_Witte_2007.pdf    

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

.