Journal article
Impaired signaling pathways on Berardinelli-Seip congenital lipodystrophy macrophages during Leishmania infantum infection
Scientific reports, Vol.14(1), 11236
05/16/2024
DOI: 10.1038/s41598-024-61663-6
PMCID: PMC11099049
PMID: 38755198
Abstract
Berardinelli-Seip congenital lipodystrophy (CGL), a rare autosomal recessive disorder, is characterized by a lack of adipose tissue. Infections are one of the major causes of CGL individuals' premature death. The mechanisms that predispose to infections are poorly understood. We used Leishmania infantum as an in vitro model of intracellular infection to explore mechanisms underlying the CGL infection processes, and to understand the impact of host mutations on Leishmania survival, since this pathogen enters macrophages through specialized membrane lipid domains. The transcriptomic profiles of both uninfected and infected monocyte-derived macrophages (MDMs) from CGL (types 1 and 2) and controls were studied. MDMs infected with L. infantum showed significantly downregulated expression of genes associated with infection-response pathways (MHC-I, TCR-CD3, and granzymes). There was a transcriptomic signature in CGL cells associated with impaired membrane trafficking and signaling in response to infection, with concomitant changes in the expression of membrane-associated genes in parasites (e.g. δ-amastins). We identified pathways suggesting the lipid storage dysfunction led to changes in phospholipids expression and impaired responses to infection, including immune synapse (antigen presentation, IFN-γ signaling, JAK/STAT); endocytosis; NF-kappaB signaling; and phosphatidylinositol biosynthesis. In summary, lipid metabolism of the host plays an important role in determining antigen presentation pathways.
Details
- Title: Subtitle
- Impaired signaling pathways on Berardinelli-Seip congenital lipodystrophy macrophages during Leishmania infantum infection
- Creators
- Viviane Brito Nogueira - Universidade Federal do Rio Grande do NorteCarolina de Oliveira Mendes-Aguiar - Instituto Federal do Rio Grande do NorteDiego Gomes Teixeira - Instituto Federal do Rio Grande do NorteFrancisco Paulo Freire-Neto - Universidade Federal do Rio Grande do NorteLeo Zenon Tassi - Universidade Federal do Rio Grande do NorteLeonardo Capistrano Ferreira - Universidade Federal do Rio Grande do NorteMary Edythe Wilson - University of IowaJosivan Gomes Lima - Hospital Universitário Onofre LopesSelma Maria Bezerra Jeronimo - Instituto Federal do Rio Grande do Norte
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.14(1), 11236
- Publisher
- NATURE PORTFOLIO
- DOI
- 10.1038/s41598-024-61663-6
- PMID
- 38755198
- PMCID
- PMC11099049
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Grant note
- #465229/2014-0 / Brazilian National Institutes of Science and Technology of Tropical Diseases Finance Code 001 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) Universal 406076/2021-9 / Brazilian National Council of Research and Technology (CNPq) I01 BX001983 / BLRD VA Merit Review grants I01 BX000536 / Department of Veterans' Affairs, USA
- Language
- English
- Date published
- 05/16/2024
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984627182302771
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