Anyone who has seen an Avengers movie knows that superhero teams consist of members with complementary strengths and weaknesses. Likewise, our immune system consists of a constellation of cell types, each with their specialized function.
When facing a foe as dangerous as the human immunodeficiency virus (HIV), two immune cell types are known to be particularly susceptible—CD4+ T-cells and macrophages, and to a smaller degree, dendritic cells (DCs).
This has been the prevailing belief until a recent study by Florent Ginhoux, a Senior Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN). Together with the team of Philippe Benaroch at the Curie Institute in Paris, Ginhoux discovered that a rare subset of DC precursors has unique properties that make them three or four times more readily infected by HIV than other DC populations.
In particular, the expression of a viral receptor called Siglec-1 on this population of DC precursors piqued the curiosity of Ginhoux’s team.
“When we discovered pre-dendritic cells (pre-DCs), we did not immediately think about HIV. But then we noticed that they showed a high expression of a molecule called Siglec-1. This triggered our interest because Siglec-1 is known to bind to HIV,” said Ginhoux.
To identify the role Siglec-1 plays in HIV infection, the researchers used an antibody to block the Siglec-1 receptor on pre-DCs. This prevented the pre-DCs from being infected by the HIV-1 virus to varying extents: 35% inhibition for CCR5-tropic strains, and 85% inhibition for CXCR4-tropic strains.
One option for stopping HIV infection would be to make pre-DCs resistant to viral fusion and replication. However, pre-DCs made resistant to viral fusion were still able to capture viral particles on their surface via Siglec-1, and transmit the virus to CD4+ T-cells in a replication-independent manner.
Nonetheless, Ginhoux thinks that the answer to stopping HIV infection and transmission is more complex than just blocking the Siglec-1 receptor—doing so would allow other infections to pass by undetected, sacrificing the immune system’s general antiviral response.
Findings from this study have broader implications for other infectious diseases, which Ginhoux’s team is keen to explore in the future. “It would be interesting to look into whether pre-DCs play a similar role in the spread of viral diseases like dengue and chikungunya,” he said.
The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN).