Biology subjects

Carroll, S. L.

Publications and source records attributed to Carroll, S. L..

3 recordsLinked to original sources

bioRxiv2025

Identification of distinct cDC2 subpopulations that direct microbiota-specific T cell differentiation

How the complex network of intestinal antigen presenting cells (APCs) instructs CD4+ T cell responses against the microbiota remains unclear. Here, we use Labeling Immune Partnerships by SorTagging Intercellular Contacts (LIPSTIC) to characterize the APCs that prime CD4+ T cells recognizing the commensal bacterium Akkermansia muciniphila. A. muciniphila-specific T cells engaged multiple transcriptionally distinct migratory cDC2 subpopulations, both at homeostasis, when A. muciniphila promotes TFH differentiation, and during inflammation, when it also drives TH1 and TH17 differentiation. The identity of these subpopulations was unchanged by inflammation; however, the distribution of presentation across the subpopulations shifted, with increased presentation by inflammatory cDC2s favoring TH1 and TH17 polarization. These results reveal how distinct T cell differentiation trajectories can be determined through varied interactions with multiple, functionally distinct subpopulations of APCs.

immunology↗

bioRxiv2024

Detecting mtDNA effects with an Extended Pedigree Model: An Analysis of Statistical Power and Estimation Bias

Mitochondrial DNA (mtDNA) plays a crucial role in numerous cellular processes, yet its impact on human behavior remains underexplored. The current paper proposes a novel covariance structure model with seven parameters to specifically isolate and quantify mtDNA effects on human behavior. This approach uses extended pedigrees to obtain estimates of mtDNA variance while controlling for other genetic and environmental influences. Our Monte-Carlo simulations indicate that a sample size of approximately 5,000 individuals is sufficient to detect medium mtDNA effects (mt2 = 5%), while a more substantial cohort of around 30,000 is required for small effects (mt2 = 1%). We show that deeper pedigrees increase power to detect the mtDNA effect while wider pedigrees decrease power, given the equal total sample size. We evaluated how missing kinship records and mtDNA mutations impact bias. Both lead to underestimation of mtDNA variance, and an overestimation of the interaction between nuclear DNA and mtDNA. In addition, the false positive rate of mtDNA effect estimation is low when fitting the model with data generated without mtDNA effects. Collectively, we demonstrate that using extended pedigrees to quantify the influence of mtDNA on human behavior is robust and powerful.

genetics↗

bioRxiv2019

Integrated Single-Cell Analysis of Multicellular Immune Dynamics during Hyper-Acute HIV-1 Infection

Cellular immunity is critical for controlling intracellular pathogens, but the dynamics and cooperativity of the evolving host response to infection are not well defined. Here, we apply single-cell RNA-sequencing to longitudinally profile pre- and immediately post-HIV infection peripheral immune responses of multiple cell types in four untreated individuals. Onset of viremia induces a strong transcriptional interferon response integrated across most cell types, with subsequent pro-inflammatory T cell differentiation, monocyte MHC-II upregulation, and cytolytic killing. With longitudinal sampling, we nominate key intra- and extracellular drivers that induce these programs, and assign their multi-cellular targets, temporal ordering, and duration in acute infection. Two individuals studied developed spontaneous viral control, associated with initial elevated frequencies of proliferating cytotoxic cells, inclusive of a previously unappreciated proliferating natural killer (NK) cell subset. Our study presents a unified framework for characterizing immune evolution during a persistent human viral infection at single-cell resolution, and highlights programs that may drive response coordination and influence clinical trajectory.

immunology↗