Visualizing the Immune System: Providing Key Insights into HIV/SIV Infections

Abstract

Immunological inductive tissues, such as secondary lymphoid organs, are composed of distinct anatomical microenvironments for the generation of immune responses to pathogens and immunogens. These microenvironments are characterized by the compartmentalization of highly specialized immune and stromal cell populations, as well as the presence of a complex network of soluble factors and chemokines that direct the intra-tissue trafficking of naïve and effector cell populations. Imaging platforms have provided critical contextual information regarding the molecular and cellular interactions that orchestrate the spatial microanatomy of relevant cells and the development of immune responses against pathogens. Particularly in HIV/SIV disease, imaging technologies are of great importance in the investigation of the local interplay between the virus and host cells, with respect to understanding viral dynamics and persistence, immune responses (i.e., adaptive and innate inflammatory responses), tissue structure and pathologies, and changes to the surrounding milieu and function of immune cells. Merging imaging platforms with other cutting-edge technologies could lead to novel findings regarding the phenotype, function, and molecular signatures of particular immune cell targets, further promoting the development of new antiviral treatments and vaccination strategies.

Intrahepatic CXCL10 is strongly associated with liver fibrosis in HIV-Hepatitis B co-infection

“…We found that sCD14 (a marker of monocyte activation) was associated with multiple markers of HIV-in both the periphery and in the liver, however this is not direct proof of Kupffer cell infection. Defining the specific cells where HIV resides in liver is needed and could potentially be addressed using fluorescent probes as recently demonstrated with RNA and DNA scope [51].…”

Single-Cell Technologies Applied to HIV-1 Research: Reaching Maturity

“…Signal amplification technologies have been developed to allow simultaneous single-cell detection of proviral vDNA and vRNA, giving valuable information both on DNA integration and viral gene expression without altering tissue structure (Deleage et al, 2018). Coupled with automated imaging of multiple tissues, these approaches have allowed rigorous assessment of anatomical compartmentalization and total body burden of SIV and HIV-1 reservoirs (Deleage et al, 2016;Estes et al, 2017Estes et al, , 2018. A variant of this method enabled detection of spliced viral RNA using probes specific for the tat-rev splice junctions, thus increasing the likelihood of detecting viral RNA + cells in situ associated with replication-competent viruses (Deleage et al, 2018).…”

Abnormal Tryptophan Metabolism in HIV and Mycobacterium tuberculosis Infection

“…Human immunodeficiency virus (HIV) is characterized by the massive loss of CD4 + T cells, functional impairment of immune cells, disruption of the lymphoid tissues, and chronic activation ( Veazey et al, 1998 ; Brenchley et al, 2006 ; Sankaran et al, 2008 ; Xu et al, 2013 ; Estes et al, 2018 ; Wang and Xu, 2018 ). Antiretroviral therapy (ART) has dramatically reduced HIV-1 replication and viremia, yet residual low-level replication-competent proviral reservoirs remain functional in a latent state, resulting in lifelong infection and viral rebound once ART is discontinued ( Barouch and Deeks, 2014 ; Ventura, 2020 ).…”