Bscl2 Deficiency Does Not Directly Impair the Innate Immune Response in a Murine Model of Generalized Lipodystrophy

Ahlima Roumane, George D Mcilroy, Arda Balci, Weiping Han, Mirela Delibegović, Massimiliano Baldassarre, Philip Newsholme, Justin J Rochford* (Corresponding Author)

*Corresponding author for this work

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Abstract

Congenital Generalized Lipodystrophy type 2 (CGL2) is the most severe form of lipodystrophy and is caused by mutations in the BSCL2 gene. Affected patients exhibit a near complete lack of adipose tissue and suffer severe metabolic disease. A recent study identified infection as a major cause of death in CGL2 patients, leading us to examine whether Bscl2 loss could directly affect the innate immune response. We generated a novel mouse model selectively lacking Bscl2 in the myeloid lineage (LysM-B2KO) and also examined the function of bone-marrow-derived macrophages (BMDM) isolated from global Bscl2 knockout (SKO) mice. LysM-B2KO mice failed to develop lipodystrophy and metabolic disease, providing a model to study the direct role of Bscl2 in myeloid lineage cells. Lipopolysaccharide-mediated stimulation of inflammatory cytokines was not impaired in LysM-B2KO mice or in BMDM isolated from either LysM-B2KO or SKO mice. Additionally, intracellular fate and clearance of bacteria in SKO BMDM challenged with Staphylococcus aureus was indistinguishable from that in BMDM isolated from littermate controls. Overall, our findings reveal that selective Bscl2 deficiency in macrophages does not critically impact the innate immune response to infection. Instead, an increased susceptibility to infection in CGL2 patients is likely to result from severe metabolic disease.

Original languageEnglish
Article number441
Number of pages10
JournalJournal of Clinical Medicine
Volume10
Issue number3
DOIs
Publication statusPublished - 23 Jan 2021

Keywords

  • BSCL2
  • seipin
  • ; congenital generalized lipodystrophy
  • immunity
  • macrophages

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