HIV transmitting mononuclear phagocytes; integrating the old and new

Abstract

In tissue, mononuclear phagocytes (MNP) are comprised of Langerhans cells, dendritic cells, macrophages and monocyte-derived cells. They are the first immune cells to encounter HIV during transmission and transmit the virus to CD4 T cells as a consequence of their antigen presenting cell function. To understand the role these cells play in transmission, their phenotypic and functional characterisation is important. With advancements in high parameter single cell technologies, new MNPs subsets are continuously being discovered and their definition and classification is in a state of flux. This has important implications for our knowledge of HIV transmission, which requires a deeper understanding to design effective vaccines and better blocking strategies. Here we review the historical research of the role MNPs play in HIV transmission up to the present day and revaluate these studies in the context of our most recent understandings of the MNP system.

An in situ quantitative map of initial human colorectal HIV transmission

“…However, the early events leading to infection remain poorly understood. DCs and macrophages facilitate HIV transfer and enhanced CD4+ T cell infection in vitro , however in situ characterisation using human tissue is lacking and mostly qualitative (Vine et al, 2022). Using our SpicyR algorithm and temporal inference we show that after HIV penetrates the EP, HIV target cells appear to move away from the EP and form clusters consisting of DCs, macrophages and CD4+ T cells ( Figure 6 ).…”

“…Blocking transmission of HIV therefore remains and high global priority which requires an effective vaccine and, in the meantime, better prophylactic interventions. To achieve these goals, we need a better understanding of the initial events that govern transmission of HIV particularly early viral interactions with antigen presenting cells such as dendritic cells (DC) and macrophages and their subsequent delivery of the virus to CD4+ T cells (Vine et al, 2022).…”

“…Concordant data has also been described in human studies (Chun et al, 1998; Colby et al, 2018). Due to technological limitations early transmission studies have been limited to time points after initial viral integration/replication (Maric et al, 2021; Stieh et al, 2016; Vine et al, 2022) or the use of model systems, with human tissue studies mostly performed on isolated cells or by imaging of limited parameters (Bertram et al, 2019a; Ganor et al, 2010; Hladik et al, 2007; Rhodes et al, 2021; Trifonova et al, 2018; Vine et al, 2022). Thus, we still do not know the initial events that lead to mucosal HIV infection in the human tissues where transmission occurs.…”

Langerin-expressing dendritic cells in pulmonary immune-related diseases

“…LCs were traditionally regarded as a subset of immature DCs residing in epidermis and other mucosal epithelia due to their comparable function and dendritic processes ( 10 , 11 ). Even though LCs are currently best classified as a type of mononuclear phagocytes (MNPs) distinct from DCs for that LCs are derived similarly to macrophages from the yolk sac during embryogenesis differently from DCs ( 12 ). According to the recent literature, we summarize the expression and distribution of langerin in the MNPs in tissue and blood of human and mouse.…”

An in situ analysis pipeline for initial host-pathogen interactions reveals signatures of human colorectal HIV transmission

“…To achieve these goals, we need a better understanding of the initial events that govern transmission of HIV, particularly early viral interactions with antigen-presenting cells, such as dendritic cells (DCs) and macrophages, and their subsequent delivery of the virus to CD4 + T cells (Vine et al, 2022).…”