Bscl2 Deficiency Does Not Directly Impair the Innate Immune Response in a Murine Model of Generalized Lipodystrophy.
Bscl2 Deficiency Does Not Directly Impair the Innate Immune Response in a Murine Model of Generalized Lipodystrophy.
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DOI：
10.3390/jcm10030441
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发表时间：
2021-01-23
影响因子：
3.9
通讯作者：
Rochford JJ
中科院分区：
文献类型：
--
作者：
Roumane A;Mcilroy GD;Balci A;Han W;Delibegović M;Baldassarre M;Newsholme P;Rochford JJ
先天性全身性脂肪营养不良2型（CGL 2）是脂肪营养不良的最严重形式，由BSCL 2基因突变引起。受影响的患者表现出几乎完全缺乏脂肪组织，并患有严重的代谢疾病。最近的一项研究确定感染是CGL 2患者死亡的主要原因，这使我们研究Bscl 2丢失是否会直接影响先天免疫反应。我们产生了一种新的小鼠模型，选择性缺乏Bscl 2的骨髓谱系（LysM-B2 KO），并检查了功能的骨髓衍生的巨噬细胞（BMDM）从全球Bscl 2敲除（SKO）小鼠分离。LysM-B2 KO小鼠没有发生脂肪营养不良和代谢疾病，提供了研究Bscl 2在髓系细胞中的直接作用的模型。在LysM-B2 KO小鼠或从LysM-B2 KO或SKO小鼠分离的BMDM中，脂多糖介导的炎性细胞因子刺激未受损。此外，用金黄色葡萄球菌攻击的SKO BMDM中细菌的细胞内命运和清除与从同窝对照中分离的BMDM中的细菌的细胞内命运和清除不可区分。总的来说，我们的研究结果表明，巨噬细胞中的选择性Bscl 2缺陷不会严重影响对感染的先天免疫反应。相反，CGL 2患者对感染的易感性增加可能是由于严重的代谢疾病。
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.
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影响因子：
8.1
作者：
Talukder MM;Sim MF;O'Rahilly S;Edwardson JM;Rochford JJ
通讯作者：
Rochford JJ
影响因子：
4.3
作者：
Remmerie A;Scott CL
通讯作者：
Scott CL
影响因子：
4.6
作者：
Sim, M. F. Michelle;Persiani, Elisa;Rochford, Justin J.
通讯作者：
Rochford, Justin J.
影响因子：
13.5
作者：
Raetzsch, Carl F.;Brooks, Natasha L.;Alderman, J. McKee;Moore, Kelli S.;Hosick, Peter A.;Klebanov, Simon;Akira, Shizuo;Bear, James E.;Baldwin, Albert S.;Mackman, Nigel;Combs, Terry P.
通讯作者：
Combs, Terry P.
影响因子：
3.7
作者：
Owen C;Czopek A;Agouni A;Grant L;Judson R;Lees EK;Mcilroy GD;Göransson O;Welch A;Bence KK;Kahn BB;Neel BG;Mody N;Delibegović M
通讯作者：
Delibegović M