Candida albicans Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis.
Candida albicans Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis.
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DOI：
10.3390/biomedicines9111567
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发表时间：
2021-10-29
期刊：
影响因子：
4.7
通讯作者：
Ahmad R
中科院分区：
文献类型：
--
作者：
Haider M;Al-Rashed F;Albaqsumi Z;Alobaid K;Alqabandi R;Al-Mulla F;Ahmad R
动脉粥样硬化是一种慢性退行性疾病，其特征是脂质致密斑块和影响动脉壁的低度炎症。泡沫巨噬细胞在动脉粥样硬化斑块的形成和低度炎症的诱导中是重要的。在由机会致病菌引起的感染中出现了充满脂质的巨噬细胞。白色念珠菌是免疫功能低下患者（包括糖尿病患者）念珠菌病的主要原因。然而，C.白念珠菌在巨噬细胞发泡和相关炎症中的作用尚不清楚。我们调查了C.白色念珠菌诱导泡沫沿着巨噬细胞中的炎症，如果是，通过何种机制。我们将THP-1巨噬细胞与热灭活的C.白色念珠菌（HKCA）。HKCA诱导巨噬细胞中的脂质蓄积，沿着炎症标志物（包括CD 11 b和CD 11 c）表达增加或IL-1β表达和分泌增加。HKCA还增加巨噬细胞中的PPARγ、CD 36和FABP 4的表达。从机制上讲，我们发现HKCA诱导的泡沫和炎性巨噬细胞表型需要FABP 4，因为通过化学抑制剂BMS 309404或小干扰RNA（siRNA）破坏巨噬细胞中的FABP 4可消除泡沫细胞形成和炎性标志物CD 11b、CD 11 c和IL-1β的表达。此外，HKCA处理的巨噬细胞显示高表达和分泌MMP-9。FABP 4的抑制导致HKA诱导的MMP-9产生的抑制。总的来说，我们的研究结果表明，C。白念珠菌通过上调FABP 4诱导巨噬细胞泡沫细胞形成、炎症和MMP-9表达，这可能构成治疗白念珠菌的新靶点。白色念珠菌诱导的动脉粥样硬化。
Atherosclerosis is a chronic degenerative disorder characterized by lipid-dense plaques and low-grade inflammation affecting arterial walls. Foamy macrophages are important in the formation of atherosclerotic plaques and the induction of low-grade inflammation. The presence of lipid-laden macrophages has occurred in infections caused by opportunistic pathogens. Candida albicans is the major cause of candidiasis in immunocompromised patients, including those with diabetes mellitus. However, the role played by C. albicans in macrophage foaming and the associated inflammation is poorly understood. We investigated whether C. albicans induces foaming along with inflammation in macrophages and, if so, by which mechanism(s). We incubated THP-1 macrophages with heat-killed C. albicans (HKCA). HKCA-induced lipid accumulation in macrophages along with increased expression of inflammatory markers, including CD11b and CD11c or expression and secretion of IL-1β. HKCA also increased the expression of PPARγ, CD36, and FABP4 in macrophages. Mechanistically, we found that the foamy and inflammatory macrophage phenotype induced by HKCA requires FABP4 because disruption of FABP4 in macrophages either by chemical inhibitor BMS309404 or small interfering RNA (siRNA) abrogated foam cell formation and expression of inflammatory markers CD11b, CD11c, and IL-1β. Furthermore, HKCA-treated macrophages displayed high expression and secretion of MMP-9. Inhibition of FABP4 resulted in suppression of HCKA-induced MMP-9 production. Overall, our results demonstrate that C. albicans induces foam cell formation, inflammation, and MMP-9 expression in macrophages via the upregulation of FABP4, which may constitute a novel therapeutic target for treating C. albicans-induced atherosclerosis.
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