Spatial Landscape of innate and adaptive immune response in Human Herpes Simplex Virus 2 Infection 4413

Abstract Description High T-cell effector-to-target ratio and increased cytolytic function are characteristics of rapid containment in asymptomatic HSV-2 infection. However, our understanding of the spatial relationship and functional influence of innate immune cells on T lymphocytes is yet to be defined. Here, we applied highly multiplexed immunophenotyping and single-cell spatial transcriptomics technologies to systematically investigate the composition, distribution, function, and interaction of various innate populations and T lymphocytes in the context of ulcer-forming or asymptomatic HSV infections. We found complex yet distinct anatomic patterns among innate and adaptive immune cells. Neutrophils, monocytes, and macrophages actively penetrated the HSV-infected epidermis, whereas T cells were rarely present in areas of active viral infection and located almost exclusively in the surrounding dermis, in contrast to the contiguous area of intact epithelial adjacent to the ulceration. Among the massive infiltration of T cells, only a fraction displayed cytolytic effector function by IFN-γ and granzyme B expression. Importantly, these T cells were located at the boundary and in close contact with subsets of innate cells, suggesting local tissue influence on antiviral immunity at the site of infection. Elucidating the mechanisms that regulate T-cell effector function and distribution could help therapeutic vaccine development to control HSV-2 infection in humans. Funding Sources NIH/NIAID AI143773, AI184778 Topic Categories Viral Immunology (VIR)