Optimizing deep learning-based segmentation of densely packed cells using cell surface markers.

Background: Spatial molecular profiling depends on accurate cell segmentation. Identification and quantitation of individual cells in dense tissues, e.g.

Tissue-Resident-Memory CD8 T Cells Bridge Innate Immune Responses in Neighboring Epithelial Cells to Control Human Genital Herpes.

Tissue-resident-memory T cells (TRM) populate the body's barrier surfaces, functioning as frontline responders against reencountered pathogens. Understanding of the mechanisms by which CD8TRM achieve effective immune protection remains incomplete in a naturally recurring human disease. Using laser capture microdissection and transcriptional profiling, we investigate the impact of CD8TRM on the tissue microenvironment in skin biopsies sequentially obtained from a clinical cohort of diverse disease expression during herpes simplex virus 2 (HSV-2) reactivation.

Distinct populations of antigen-specific tissue-resident CD8+ T cells in human cervix mucosa.

The ectocervix is part of the lower female reproductive tract (FRT), which is susceptible to sexually transmitted infections (STIs). Comprehensive knowledge of the phenotypes and T cell receptor (TCR) repertoire of tissue-resident memory T cells (TRMs) in the human FRT is lacking. We took single-cell RNA-Seq approaches to simultaneously define gene expression and TCR clonotypes of the human ectocervix.

B cells, antibody-secreting cells, and virus-specific antibodies respond to herpes simplex virus 2 reactivation in skin.

Tissue-based T cells are important effectors in the prevention and control of mucosal viral infections; less is known about tissue-based B cells. We demonstrate that B cells and antibody-secreting cells (ASCs) are present in inflammatory infiltrates in skin biopsy specimens from study participants during symptomatic herpes simplex virus 2 (HSV-2) reactivation and early healing. Both CD20+ B cells, most of which are antigen inexperienced based on their coexpression of IgD, and ASCs - characterized by dense IgG RNA expression in combination with CD138, IRF4, and Blimp-1 RNA - were found to colocalize with T cells.

High Community SARS-CoV-2 Antibody Seroprevalence in a Ski Resort Community, Blaine County, Idaho, US. Preliminary Results.

Community-level seroprevalence surveys are needed to determine the proportion of the population with previous SARS-CoV-2 infection, a necessary component of COVID-19 disease surveillance. In May, 2020, we conducted a cross-sectional seroprevalence study of IgG antibodies for nucleocapsid of SARS-CoV-2 among the residents of Blaine County, Idaho, a ski resort community with high COVID-19 attack rates in late March and Early April (2.9% for ages 18 and older).

Keratinocytes produce IL-17c to protect peripheral nervous systems during human HSV-2 reactivation.

Despite frequent herpes simplex virus (HSV) reactivation, peripheral nerve destruction and sensory anesthesia are rare. We discovered that skin biopsies obtained during asymptomatic human HSV-2 reactivation exhibit a higher density of nerve fibers relative to biopsies during virological and clinical quiescence. We evaluated the effects of HSV infection on keratinocytes, the initial target of HSV replication, to better understand this observation.

Immune surveillance by CD8αα+ skin-resident T cells in human herpes virus infection.

Most herpes simplex virus 2 (HSV-2) reactivations in humans are subclinical and associated with rapid expansion and containment of virus. Previous studies have shown that CD8(+) T cells persist in genital skin and mucosa at the dermal-epidermal junction (DEJ)--the portal of neuronal release of reactivating virus--for prolonged time periods after herpes lesions are cleared. The phenotype and function of this persistent CD8(+) T-cell population remain unknown.

An effector phenotype of CD8+ T cells at the junction epithelium during clinical quiescence of herpes simplex virus 2 infection.

Herpes simplex virus 2 infection is characterized by cycles of viral quiescence and reactivation. CD8(+) T cells persist at the site of viral reactivation, at the genital dermal-epidermal junction contiguous to neuronal endings of sensory neurons, for several months after herpes lesion resolution. To evaluate whether these resident CD8(+) T cells frequently encounter HSV antigen even during times of asymptomatic viral infection, we analyzed the transcriptional output of CD8(+) T cells captured by laser microdissection from human genital skin biopsy specimens during the clinically quiescent period of 8 weeks after lesion resolution.

Evasion of the mucosal innate immune system by herpes simplex virus type 2.

Understanding the mechanisms by which herpes simplex virus (HSV) evades host immune defenses is critical to defining new approaches for therapy and prevention. We performed transcriptional analyses and immunocytochemistry on sequential biopsy specimens of lesional tissue from the acute through the posthealing phases of recurrent mucocutaneous HSV-2 infection. Histological analysis of these biopsy specimens during the acute stage revealed a massive infiltration of T cells, as well as monocytes/macrophages, a large amount of myeloid, and a small number of plasmacytoid dendritic cells, in the dermis of these lesional biopsy specimens.