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Study of visceral leishmaniasis establishment - Gene expression from (un)infected (non-)vaccinated mouse spleen samples

ABSTRACT: Visceral leishmaniasis (VL) caused by Leishmania donovani and L. infantum is a potentially fatal disease. To date there are no registered vaccines for disease prevention despite the fact that several vaccines are in preclinical development. Thus, new strategies are needed to improve vaccine efficacy based on a better understanding of the mechanisms mediating protective immunity and mechanisms of host immune responses subversion by immunopathogenic components of Leishmania. In the present study, determination of the immune mechanisms related to infection or protective immune responses against VL using an experimental nanovaccine as a vaccine model was conducted through microarray analysis.

ORGANISM(S): Mus musculus

PROVIDER: GSE134661 | GEO | 2019/11/19

REPOSITORIES: GEO

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Project description:While dendritic cells (DCs) are known to play a major role in the process of vaccination, the mechanisms by which vaccines induce protective immunity in humans remain elusive. Herein, we used gene microarrays to characterize the transcriptional programs induced over time in human monocyte-derived DCs (moDCs) in vitro in response to influenza H1N1 Brisbane, Salmonella enterica and Staphylococcus aureus. We built a data-driven modular analytical framework focused on 204 pathogen-induced gene clusters. The expression of these modules was analyzed in response to 16 well-defined ligands, targeting TLRs, cytoplasmic PAMP receptors and cytokine receptors. This multi-dimensional framework covers the major biological functions of APC, including the IFN response, inflammation, DC maturation, T cell activation, antigen processing, cell motility and histone regulation. This framework was used to characterize the response of monocytes and moDCs to 14 commercially available vaccines. These vaccines displayed quantitatively and qualitatively distinct modular signatures in monocytes and DCs, in particular Fluzone and Pneumovax, highlighting the functional and phenotypic differences between APC subsets. This modular framework allows the application of systems immunology approaches to study early transcriptional changes in human APC subsets in response to pathogens and vaccines, which might guide the development of improved vaccines. 64 samples of IL4 DC, and 64 samples of monocytes stimulated by media (controls, designated 1 and 2 to indicate biological replicates), Menomune (Neisseiria meningitis vaccine, MGL), Fluzone 09-10 (Influenza vaccine, FZ), Havrix (Hepatitis A vaccine, HEPA), Ixiaro (Japanese encephalitis vaccine, JPE), ActHib (Haemophilus influenza vaccine, HIB) and Pneumovax (Pneumococcus vaccine, PVX), Engerix-B (Hepatitis B vaccine, HEPB), Zostavax (Herpes Zoster vaccine, HER), and Gardasil (Human Papilloma virus vaccine, HPV), LPS, Ipol (Polio vaccine, POL), Rabies vaccine (RAB), toxoid-based vaccine (TDAP), Varivax (Varicella vaccine, VAR)

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Study of visceral leishmaniasis establishment - Gene expression from (un)infected (non-)vaccinated mouse spleen samples

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