Biology subjects

Farris, A. D.

Publications and source records attributed to Farris, A. D..

2 recordsLinked to original sources

bioRxiv2025

Persistent CD4+ T cell functional deficits during recovery from prolonged symptomatic SARS-CoV-2 infection

Symptoms of acute SARS-CoV-2 infection often resolve quickly but are sometimes associated with persistent immune dysfunction. The factors that predispose individuals to compromised immune function have not been well defined. We investigated CD4+ T cell phenotype and function in a small cohort of individuals who recovered from mild to moderate SARS-CoV-2 infection without hospitalization and were divided into short or prolonged symptom duration groups. Five individuals with prolonged symptom duration showed marked downregulation of CD4 on CD3+CD8- T cells (CD4low group) and a poor response to TCR stimulation with the superantigen Staphylococcal enterotoxin B (SEB), as shown by weak upregulation of the activation markers CD134 and CD69. CD4 surface intensities recovered to normal levels in four of these individuals within 3-12 months. Selected cytokines (IL-1RA, IL-7, and VEGF) were elevated in individuals with low CD4, but plasma levels of anti-S1 IgG did not correlate with CD4 defects. Bulk RNA sequencing of unstimulated and SEB-treated CD3+CD8- T cells revealed a >50% reduction in the number of differentially expressed genes in the CD4low group compared to the same individuals after CD4 levels were recovered and a healthy control group. Upstream regulator analysis of differentially expressed genes in unstimulated CD4low cells suggested a response to IFN, while SEB-stimulated CD4low cells showed reduced functionality of IL-2, CD28, and SATB1 regulated pathways. In summary, prolonged symptomatic recovery from SARS-CoV-2 infection was associated with a global CD4+ T cell response defect, defined by low surface CD4 expression, evidence of IFN signaling, and defective T cell activation.

immunology↗

bioRxiv2023

Peptidoglycan from Bacillus anthracis Inhibits Human Macrophage Efferocytosis in Part by Reducing Cell Surface Expression of MERTK and TIM-3

Bacillus anthracis peptidoglycan (PGN) is a major component of the bacterial cell wall and a key pathogen-associated molecular pattern (PAMP) contributing to anthrax pathology, including organ dysfunction and coagulopathy. Increases in apoptotic lymphocytes are a late-stage feature of anthrax and sepsis, suggesting there is a defect in apoptotic clearance. Here, we tested the hypothesis that B. anthracis PGN inhibits the capacity of human monocyte-derived macrophages (M{Phi}) to efferocytose apoptotic cells. Exposure of CD163+CD206+ M{Phi} to PGN for 24h impaired efferocytosis in a manner dependent on human serum opsonins but independent of complement component C3. PGN treatment reduced cell surface expression of the pro-efferocytic signaling receptors MERTK, TYRO3, AXL, integrin V{beta}5, CD36 and TIM-3, whereas TIM-1, V{beta}3, CD300b, CD300f, STABILIN-1 and STABILIN-2 were unaffected. ADAM17 is a major membrane-bound protease implicated in mediating efferocytotic receptor cleavage. We found multiple ADAM17-mediated substrates increased in PGN-treated supernatant suggesting involvement of membrane-bound proteases. ADAM17 inhibitors TAPI-0 and Marimastat prevented TNF release, indicating effective protease inhibition, and modestly increased cell-surface levels of MerTK and TIM-3 but only partially restored efferocytic capacity by PGN-treated M{Phi}. We conclude that human serum factors are required for optimal recognition of PGN by human M{Phi} and that B. anthracis PGN inhibits efferocytosis in part by reducing cell surface expression of MERTK and TIM-3.

immunology↗