Project description:The continuously remodeled extracellular matrix (ECM) plays a pivotal role in gastrointestinal health and disease, yet its precise functions remain elusive. In this project, we employed laser capture microdissection of cecal mucosa combined with low-input proteomics to investigate ECM remodeling during Salmonella-driven inflammation. To complement this, we probed how fibronectin fiber tension is altered using a mechanosensitive peptide probe. While fibronectin fibers in healthy intestinal tissue are typically stretched, fibronectin fiber relaxation occurred exclusively during late-stage infection at 72 hours and was localized to already existing clusters of infiltrated neutrophils in the cecal mucosa of Salmonella-infected mice.
2025-05-07 | PXD056083 | Pride
Project description:Microbial sequencing of piglet intestinal mucosa
Project description:Salmonella enterica serotype Typhimurium causes an acute inflammatory reaction in the cecum of streptomycin pre-treated mice. We determined global changes in gene expression elicited by serotype Typhimurium in the cecal mucosa. The gene expression profile was dominated by T cell derived cytokines and genes whose expression is known to be induced by these cytokines. Markedly increased mRNA levels of interferon (IFN) ï§, interleukin (IL) 22 and IL-17 were detected by quantitative real-time PCR. Furthermore, mRNA levels of genes whose expression is induced by IFNï§, IL-22 or IL-17, including macrophage inflammatory protein (MIP)-2, inducible nitric oxide synthase (iNOS), lipocalin-2, MIP-1ï¡, MIP-1ï¢, and keratinocyte-derived cytokine (KC), were also markedly increased. To assess the importance of T cells in orchestrating this pro-inflammatory gene expression profile, we depleted T cells using a monoclonal antibody prior to investigating cecal inflammation caused by serotype Typhimurium in streptomycin pre-treated mice. Depletion of CD3+ T cells resulted in a dramatic reduction in gross pathology, a significantly reduced recruitment of neutrophils and a marked reduction in mRNA levels of IFNï§, IL-22, IL-17, iNOS, lipocalin-2 and KC. Our results suggest that T cells play an important role in amplifying inflammatory responses induced by serotype Typhimurium in the cecal mucosa. Experiment Overall Design: Determine global changes in gene expression elicited by serotype Typhimurium in the cecal mucosa. For each condition, control and infected, total cecal RNA from 4 mice was pooled
Project description:Salmonella enterica serotype Typhimurium causes an acute inflammatory reaction in the cecum of streptomycin pre-treated mice. We determined global changes in gene expression elicited by serotype Typhimurium in the cecal mucosa. The gene expression profile was dominated by T cell derived cytokines and genes whose expression is known to be induced by these cytokines. Markedly increased mRNA levels of interferon (IFN-gamma), interleukin-22 (IL-22) and IL-17 were detected by quantitative real-time PCR. Furthermore, mRNA levels of genes whose expression is induced by IFN-gamma, IL-22 or IL-17, including macrophage inflammatory protein 2 (MIP-2), inducible nitric oxide synthase (Nos2), lipocalin-2, MIP-1alpha, MIP-1beta, and keratinocyte-derived cytokine (KC), were also markedly increased. To assess the importance of T cells in orchestrating this pro-inflammatory gene expression profile, we depleted T cells using a monoclonal antibody prior to investigating cecal inflammation caused by serotype Typhimurium in streptomycin pre-treated mice. Depletion of CD3+ T cells resulted in a dramatic reduction in gross pathology, a significantly reduced recruitment of neutrophils and a marked reduction in mRNA levels of IFN-gamma, IL-22, IL-17, iNOS, lipocalin-2 and KC. Our results suggest that T cells play an important role in amplifying inflammatory responses induced by serotype Typhimurium in the cecal mucosa. Keywords: Disease state analysis
Project description:Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis while pediatric patients with severe Plasmodium falciparum malaria can develop a life threatening bacteremia that is a major source of child mortality in sub-Saharan Africa. We used microarrays to detail genome-scale gene expression profiles underlying gastrointestinal immune responses to bacterial infection in mice Responses were measured in mouse cecal mucosa to infection of non-typhodal Salmonella and Plasmodium yoelii, both singularly and in combination.