Efficient transfer of HIV-1 in trans and in cis from Langerhans dendritic cells and macrophages to autologous T lymphocytes.
OBJECTIVE
The chronology of HIV infection in mucosal tissue after sexual transmission is unknown. Several potential HIV target cells are present at these sites, including dendritic cells, macrophages, and CD4(+) T lymphocytes. Dendritic cells and macrophages are antigen-presenting cells (APCs) and are thus involved in cross-talk with T cells. This close contact may favor efficient HIV-1 transfer to T lymphocytes, resulting in rapid HIV-1 dissemination.


METHODS
We investigated the role of APCs in HIV transfer to T cells by incubating Langerhans cells and interstitial dendritic cells (IDCs) or monocyte-derived macrophages (MDMs) with HIV for 2 h before addition of uninfected autologous CD4(+) T lymphocytes.


METHODS
HIV infection was recorded after different time points. Following staining, the measurement of intracellular p24 in the different cell populations was analyzed by flow cytometry.


RESULTS
We showed that Langerhans cells/IDCs and macrophages efficiently transferred HIV to CD4(+) T cells. Interestingly, a rapid HIV transfer in trans predominated in MDMs, whereas cis transfer mainly occurred in Langerhans cells/IDC cocultures. Neutralizing antibody 2G12, added to HIV-loaded APCs, efficiently blocked both the trans and the cis infection of T cells.


CONCLUSIONS
These findings highlight the major contributions of various mucosal cells in HIV dissemination and suggest that HIV hijacks the different properties of APCs to favor its dissemination through the body. They emphasize the role of macrophages in the rapid transmission of HIV to T lymphocytes at mucosal sites, dendritic cells being prone to migration to lymphoid organ for subsequent dissemination by cis transfer.
INSERM U1110, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France. *Vincent Holl deceased.
Maryse
M
Peressin
Alizé
A
Proust
Sylvie
S
Schmidt
Bin
B
Su
Mélanie
M
Lambotin
Marina E
ME
Biedma
Géraldine
G
Laumond
Thomas
T
Decoville
Vincent
V
Holl
Christiane
C
Moog
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000821:virology*; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007231:Infant, Newborn; D008264:Macrophages / Q000821:virology*; D013997:Time Factors
D016655:HIV Core Protein p24