Project description:Microsporidia are single-celled intracellular parasites that cause opportunistic diseases in humans. Encephalitozoon intestinalis is a prevalent human-infecting species that invades the small intestine. Dissemination to other organ systems is also observed, and is potentially facilitated by macrophages. The macrophage response to infection and the developmental trajectory of the parasite are not well studied. Here we use single cell RNA sequencing to investigate transcriptional changes in both the host and parasite during infection. While a small population of infected macrophages mount a response, most remain transcriptionally unchanged, suggesting that the majority of parasites may avoid host detection. The parasite transcriptome reveals large transcriptional changes throughout the life cycle, providing a blueprint for parasite development. The stealthy microsporidian lifestyle likely allows these parasites to harness macrophages for replication and dissemination. Together, our data provide insights into the host response in primary human macrophages and the E. intestinalis developmental program.
Project description:In order to study the molecular response of human foreskin fibroblast (HFF) cells to E. cuniculi parasite infection, kinetics microarray experiments targeting human genes expression have been performed during the parasite whole infection cycle. Infected HFF cells (IHFF; t=4h, 16h, 48h, 72h and 120h ) were systematically compared with control uninfected HFF cells (UHFF; t=0h).
Project description:In order to study the molecular response of human foreskin fibroblast (HFF) cells to E. cuniculi parasite infection, kinetics microarray experiments targeting human genes expression have been performed during the parasite whole infection cycle. Infected HFF cells (IHFF; t=4h, 16h, 48h, 72h and 120h ) were systematically compared with control uninfected HFF cells (UHFF; t=0h). Time-dependent experiment comparing two conditions, IHFF vs. UHFF cells (data points: t=4h/0h, t=16h/0h, t=48h/0h, t=72h/0h, t=120h/0h).
Project description:Cerebral Malaria (CM), the deadliest complication of Plasmodium infection, is a complex and unpredictable disease. Currently, our understanding of the factors that trigger progression of malaria to CM is limited. Here, by infecting experimental CM (ECM) resistant (Balb/c) and ECM susceptible (C57BL/6) mice with ECM causing (ANKA) and non-ECM causing (NK65) Plasmodium berghei (Pb) parasite strains, we revealed that in resistant host, infection by ECM causing parasite develops similar to infection by non-ECM causing parasite in susceptible host in terms of parasite growth in host, disease course and host immune response against parasite. Our comparative gene expression analysis revealed that in Balb/c host, gene expression of Pb ANKA parasite is remarkably different from, the gene expression of Pb ANKA in C57BL/6 but similar to the gene expression of non-ECM causing Pb NK65 in C57BL/6. Thus, host has a critical influence on parasite behavior which ultimately determines the course of malaria disease.
Project description:Sjogren's syndrome is an autoimmune disease, characterized by complaints such as xerostomia and keratoconjunctivitis sicca. In other autoimmune diseases such as diabetes and SLE, monocyte abberancies have been described. Therefore, this study aimed at studying the monocyte compartment in Sjogren's Syndrome, by transcription profiling of CD14+CD16- and CD14lowCD16+ monocytes in patients and controls.
Project description:Comprehensive proteomic analysis of the protein expression landscape of bronchoalveolar lavage fluid during invasive pulmonary aspergillosis in murine and human samples. 38 murine BALF samples (10 Aspergillus fumigatus infected mice without immunosuppression and without invasive pulmonary aspergillosis (IPA), 19 immunosuppressed and infected mice with IPA and 9 immunosuppressed animals without infection) were analysed for their global protein expression. In addition, 54 human BALF specimen from patients with probable IPA (23 samples), proven IPA (4 cases) and 27 control samples from patients with unrelated pulmonary diseases were analysed for their global protein composition. Host responses and Aspergillus fumigatus-specific proteins detectable in BALF were studied.