Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection.

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8+ and CD4+ T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation. Profiles of IR metrics in ~48,500 individuals collectively indicate that some persons resist degradation of IR both during aging and when challenged with varied inflammatory stressors. With this resistance, preservation of optimal IR tracked (i) a lower risk of HIV acquisition, AIDS development, symptomatic influenza infection, and recurrent skin cancer; (ii) survival during COVID-19 and sepsis; and (iii) longevity. IR degradation is potentially reversible by decreasing inflammatory stress. Overall, we show that optimal IR is a trait observed across the age spectrum, more common in females, and aligned with a specific immunocompetence-inflammation balance linked to favorable immunity-dependent health outcomes. IR metrics and mechanisms have utility both as biomarkers for measuring immune health and for improving health outcomes.

Flow cytometric quantification of bacteria in vaginal swab samples self-collected by adolescents attending a gynecology clinic.

Bacterial vaginosis (BV) is an important risk factor in reproductive health outcomes, such as pre-term birth and sexually transmitted infections including HIV. However, its etiology, diagnosis and treatment remain poorly defined. We evaluated flow cytometry as a tool to quantify total bacterial cells in vaginal specimens self-collected longitudinally by adolescents. BV was diagnosed by Gram-stain (criteria of Hay and Ison). Average flow cytometric counts of bacterial cell-units (BCU) was log(10) 8.04 per gram sample and was found to correlate with sample weight (p<0.0001). BV was frequently observed in this group, with 22 of 32 participants (69%) diagnosed with BV for at least one timepoint. Surprisingly, increased BCU was associated with normal Hay-Ison score (p=0.0003), even when adjusting for sample weight (p=0.02). Since presence and quantity of Lactobacillus defines normal vaginal microbiology (ie. absence of BV), this result indicates a possible bias towards dominance of Lactobacillus cells in measurements of "total" BCU. Increased BCU per gram was associated in multivariate analysis with longer self-reported time since last menstruation (p=0.004) and last sexual intercourse (p=0.007). Sperm was detected in 3 samples provided by those reporting sexual intercourse in the previous 24 h. Light-scattering profiles of bacteria and vaginal cells in samples collected over time from an individual were often identical and distinct from other individuals. To our knowledge, this is the first description of flow cytometry for analysis of commensal bacteria in vaginal specimens. Further development may help to illuminate the complex dynamics of vaginal microbial communities underlying BV.