Specific and cumulative infection burden and mild cognitive impairment and dementia: A population-based study.

Infection by pathogenic microbes is widely hypothesized to be a risk factor for the development of neurocognitive disorders and dementia, but evidence remains limited. We analyzed the association of seropositivity to 11 common pathogens and cumulative infection burden with neurocognitive disorder (mild cognitive impairment and dementia) in a population-based cohort of 475 older individuals (mean age = 67.6 y) followed up over 3-5 years for the risk of MCI-dementia. Specific seropositivities showed a preponderance of positive trends of association with MCI-dementia, including for Plasmodium, H. pylori, and RSV (p < 0.05), as well as Chickungunya, HSV-2, CMV and EBV (p > 0.05), while HSV-1 and HHV-6 showed equivocal or no associations, and Dengue and VZV showed negative associations (p < 0.05) with MCI-dementia. High infection burden (5 + cumulated infections) was significantly associated with an increased MCI-dementia risk in comparison with low infection burden (1-3 cumulative infections), adjusted for age, sex, and education. Intriguingly, for a majority (8 of 11) of pathogens, levels of antibody titers were significantly lower in those with MCI-dementia compared to cognitive normal individuals. Based on our observations, we postulate that individuals who are unable to mount strong immunological responses to infection by diverse microorganisms, and therefore more vulnerable to infection by greater numbers of different microbial pathogens or repeated infections to the same pathogen in the course of their lifetime are more likely to develop MCI or dementia. This hypothesis should be tested in more studies.

From Genesis to Old Age: Exploring the Immune System One Cell at a Time with Flow Cytometry.

The immune system is a highly complex and tightly regulated system that plays a crucial role in protecting the body against external threats, such as pathogens, and internal abnormalities, like cancer cells. It undergoes development during fetal stages and continuously learns from each encounter with pathogens, allowing it to develop immunological memory and provide a wide range of immune protection. Over time, after numerous encounters and years of functioning, the immune system can begin to show signs of erosion, which is commonly named immunosenescence. In this review, we aim to explore how the immune system responds to initial encounters with antigens and how it handles persistent stimulations throughout a person's lifetime. Our understanding of the immune system has greatly benefited from advanced technologies like flow cytometry. In this context, we will discuss the valuable contribution of flow cytometry in enhancing our knowledge of the immune system behavior in aging, with a specific focus on T-cells. Moreover, we will expand our discussion to the flow cytometry-based assessment of extracellular vesicles, a recently discovered communication channel in biology, and their implications for immune system functioning.

Systematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a prototypic endocrine autoimmune disease resulting from an immune-mediated destruction of pancreatic insulin-secreting ß  cells. A comprehensive immune cell phenotype evaluation in T1DM has not been performed thus far at the single-cell level. METHODS: In this cross-sectional analysis, we generated a single-cell transcriptomic dataset of peripheral blood mononuclear cells (PBMCs) from 46 manifest T1DM (stage 3) cases and 31 matched controls. RESULTS: We surprisingly detected profound alterations in circulatory immune cells (1784 dysregulated genes in 13 immune cell types), far exceeding the count in the comparator systemic autoimmune disease SLE. Genes upregulated in T1DM were involved in WNT signaling, interferon signaling and migration of T/NK cells, antigen presentation by B cells, and monocyte activation. A significant fraction of these differentially expressed genes were also altered in T1DM pancreatic islets. We used the single-cell data to construct a T1DM metagene z-score (TMZ score) that distinguished cases and controls and classified patients into molecular subtypes. This score correlated with known prognostic immune markers of T1DM, as well as with drug response in clinical trials. CONCLUSIONS: Our study reveals a surprisingly strong systemic dimension at the level of immune cell network in T1DM, defines disease-relevant molecular subtypes, and has the potential to guide non-invasive test development and patient stratification.