Women worldwide acquire HIV through sexual intercourse. However, the mechanisms responsible for protection or establishment of HIV infection in the genital mucosa are poorly understood. Our research focuses on identifying the mucosal immune responses that prevent (or promote) HIV infection. We are particularly interested in characterizing the initial innate responses that take place after HIV challenge. We use human tissues from hysterectomies to isolate immune cells and evaluate immune responses to HIV in vitro.
Using confocal microscopy, live-cell imaging and in vitro infection and functional assays, we recently discovered (Barr et al, 2018) that genital neutrophils release neutrophil extracellular traps (NETs) to inactivate HIV and prevent infection of HIV target cells (Figure 1). We are now investigating the underlying mechanisms responsible for NET release and HIV inactivation.
Figure 1. Neutrophil Extracellular Traps (NETs) consist of extracellular DNA structures coated with granular proteins. The image shows long extracellular DNA strands (red) coated with myeloperoxidase (blue). The membrane of purified genital neutrophils is labeled with CD15 (green). This image was featured on the cover of the September, 2018 issue of Mucosal Immunology.
An important component of our research is understanding how mucosal immune responses change as women age. We have previously reported that aging and menopause modify the distribution of genital Th17 cells (Rodriguez-Garcia et al. 2014), tissue resident CD8+ T cells and dendritic cells (Rodriguez-Garcia et al. 2018). We are now investigating how age-related changes affect mucosal immune protection against HIV.