HIV NETs

Rodriguez-Garcia Lab Research

The Rodriguez-Garcia lab focuses on understanding mucosal acquisition of HIV in women. In particular, we are interested in defining the early innate immune responses that protect against infection in the female genital mucosa, and how these responses are modified as women age. Our studies integrate the many aspects that influence mucosal protection in the genital tract, including age, hormonal fluctuations, tissue environment and pathogen/microbiome exposure, which make the study of this mucosal surface unique and challenging. Our research is currently focused on multiple projects characterizing the role of tissue neutrophils, dendritic cells, and innate lymphoid cells in mucosal HIV acquisition. Our overarching goal is to aid the development of HIV prevention strategies by identifying the critical immune protective mechanisms against HIV infection in the mucosa.

Immune Protection in the Female Genital Mucosa

HIV Acquisition in Women

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. We are now investigating the underlying mechanisms responsible for NET release and HIV inactivation (Moreno de Lara et al. 2023).

Aging Modifies Mucosal Immune Responses

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 memory T cells (Rodriguez-Garcia et al. 2018 & 2020), dendritic cells and doble negative T cells (Parthasarathy et al, 2023). We are now investigating how age-related changes affect mucosal immune protection against HIV and recently described that neutrophil responses decline with aging (Moreno de Lara et al. 2023)

Funding