Project description:The goal of this study was to define the regulation of Tfh cell response during intestinal helminth infection. Using the helminth Trichuris muris, we performed RNA-seq analysis on Tfh cells that develop during acute vs chronic helminth infection. We found that the transcriptomic profile of acute vs chronic induced Tfh cells are distinct and they express Th2/Th1-associated genes, respectively.
Project description:The goal of this study was to define the regulation of Tfh cell response during intestinal helminth infection. Using the helminth Trichuris muris, we performed ATAC-seq analysis on Tfh cells that develop during acute vs chronic helminth infection. We found that the epigenetic profile of acute vs chronic induced Tfh cells are distinct by adopting Th2 and Th1 cell phenotypes, respectively. For example, Th2-associated genes such as the Il4 locus was more accessible in acute-induced Tfh cells (and vice versa for Th1-associated genes in chronic-induced Tfh cells).
Project description:Distinct subsets of T lymphocytes express CX3CR1 under inflammatory conditions, but little is known about CX3CR1+ CD4+ T cells during Type 2 inflammation in helminth infections. Here, we used a fate-mapping mouse model to characterize CX3CR1+ CD4+ T cells during both acute Nippostrongylus brasiliensis and chronic Schistosoma mansoni helminth infections, revealing CX3CR1+ CD4+ T cells to be an activated tissue homing subset with varying capacity for cytokine production. Tracking these cells over time revealed that maintenance of CX3CR1 itself along with a TH2 phenotype conferred a survival advantage in the inflamed tissue. Single-cell RNA-sequencing analysis of fate-mapped CX3CR1+ CD4+ T cells from both the peripheral tissue and the spleen revealed a considerable level of diversity and identified a distinct population of BCL6+ TCF-1+ PD1+ CD4+ T cells in the spleen during helminth infections. Conditional deletion of BCL6 in CX3CR1+ cells result in fewer CX3CR1+ CD4+ during infection, indicating a role in sustaining CD4+ T cell responses to helminth infections. Overall, our studies revealed the behavior and heterogeneity of CX3CR1+ CD4+ T cells during Type 2 inflammation in helminth infections and identified BCL6 to be important in their maintenance
Project description:The purpose of this study was to determine differences in gene expression profiles between proliferating memory Tfh cells from elite controller (EC) and chronic aviremic HIV-infected treated (CA) individuals. We have observed significant changes in the gene expression profile between memory Tfh cells from these two patient groups and the data suggests that memory Tfh cells from CA subjects have increased IL-2 mediated signaling and are polarized towards a Th1 phenotype.
Project description:Differential gene expression profile of Tfh and non-Tfh cells from both Wt and miR-155-/- mice spleens. Wt and miR-155-/- mice were immunized with OVA. 8 days post immunization, CD4+CXCR+PD1+ Tfh cells and CD4+CXCR5-PD1- non Tfh cells were sorted from mice spleens for analyses.
Project description:T follicular helper (Tfh) cells, essential for germinal center reactions, are not identical, with different phenotypes reported. Whether, when and how they generate memory cells are still poorly understood. Here, through single-cell RNA-sequencing analysis of CXCR5+Bcl6+ Tfh cells generated under different conditions, we discovered, in addition to PD-1hi effector Tfh cells, a CD62L+PD1low subpopulation. CD62L-expressing Tfh cells developed independently from PD-1+ cells, and not in direct contact with B cells. More importantly, CD62L+ Tfh cells expressed memory- and stemness-associated genes; with more superior long-term survival, they readily generated PD-1hi cells in the recall response. Finally, KLF2 and IL7R, also highly expressed by CD62L+ Tfh cells, were required to regulate their development. Our work thus demonstrates a novel Tfh memory-like cell subpopulation, which may benefit our understanding on immune responses and diseases.
Project description:Purpose: Helminth infection and dietary intake can affect the intestinal microbiota, as well as the immune system. Methods: Here we analyzed the relationship between fecal microbiota and blood profiles of indigenous Malaysians, referred to locally as Orang Asli, in comparison to urban participants from the capital city of Malaysia, Kuala Lumpur. Results: We found that helminth infections had a larger effect on gut microbial composition than did dietary intake or blood profiles. Trichuris trichiura infection intensity also had the strongest association with blood transcriptional profiles. By characterizing paired longitudinal samples collected before and after deworming treatment, we determined that changes in serum zinc and iron levels among the Orang Asli were driven by changes in helminth infection status, independent of dietary metal intake. Serum zinc and iron levels were associated with changes in the abundance of several microbial taxa. Conclusions: There is considerable interplay between helminths, micronutrients and the microbiota on the regulation of immune responses in humans.