<i>Candida albicans</i> Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis

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 macrophage...

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Autores principales:	Mohammed Haider, Fatema Al-Rashed, Zahraa Albaqsumi, Khaled Alobaid, Rawan Alqabandi, Fahd Al-Mulla, Rasheed Ahmad
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>C. albicans</i> macrophages fat accumulation inflammation MMP-9 FABP4 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/53e7f4143abc438fb7559d80b642e863
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spelling	oai:doaj.org-article:53e7f4143abc438fb7559d80b642e8632021-11-25T16:49:09Z<i>Candida albicans</i> Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis10.3390/biomedicines91115672227-9059https://doaj.org/article/53e7f4143abc438fb7559d80b642e8632021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1567https://doaj.org/toc/2227-9059Atherosclerosis 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. <i>Candida albicans</i> is the major cause of candidiasis in immunocompromised patients, including those with diabetes mellitus. However, the role played by <i>C. albicans</i> in macrophage foaming and the associated inflammation is poorly understood. We investigated whether <i>C. albicans</i> induces foaming along with inflammation in macrophages and, if so, by which mechanism(s). We incubated THP-1 macrophages with heat-killed <i>C. albicans</i> (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 <i>C. albicans</i> 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 <i>C. albicans</i>-induced atherosclerosis.Mohammed HaiderFatema Al-RashedZahraa AlbaqsumiKhaled AlobaidRawan AlqabandiFahd Al-MullaRasheed AhmadMDPI AGarticle<i>C. albicans</i>macrophagesfat accumulationinflammationMMP-9FABP4Biology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1567, p 1567 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>C. albicans</i> macrophages fat accumulation inflammation MMP-9 FABP4 Biology (General) QH301-705.5
spellingShingle	<i>C. albicans</i> macrophages fat accumulation inflammation MMP-9 FABP4 Biology (General) QH301-705.5 Mohammed Haider Fatema Al-Rashed Zahraa Albaqsumi Khaled Alobaid Rawan Alqabandi Fahd Al-Mulla Rasheed Ahmad <i>Candida albicans</i> Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis
description	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. <i>Candida albicans</i> is the major cause of candidiasis in immunocompromised patients, including those with diabetes mellitus. However, the role played by <i>C. albicans</i> in macrophage foaming and the associated inflammation is poorly understood. We investigated whether <i>C. albicans</i> induces foaming along with inflammation in macrophages and, if so, by which mechanism(s). We incubated THP-1 macrophages with heat-killed <i>C. albicans</i> (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 <i>C. albicans</i> 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 <i>C. albicans</i>-induced atherosclerosis.
format	article
author	Mohammed Haider Fatema Al-Rashed Zahraa Albaqsumi Khaled Alobaid Rawan Alqabandi Fahd Al-Mulla Rasheed Ahmad
author_facet	Mohammed Haider Fatema Al-Rashed Zahraa Albaqsumi Khaled Alobaid Rawan Alqabandi Fahd Al-Mulla Rasheed Ahmad
author_sort	Mohammed Haider
title	<i>Candida albicans</i> Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis
title_short	<i>Candida albicans</i> Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis
title_full	<i>Candida albicans</i> Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis
title_fullStr	<i>Candida albicans</i> Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis
title_full_unstemmed	<i>Candida albicans</i> Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis
title_sort	<i>candida albicans</i> induces foaming and inflammation in macrophages through fabp4: its implication for atherosclerosis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/53e7f4143abc438fb7559d80b642e863
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<i>Candida albicans</i> Induces Foaming and Inflammation in Macrophages through FABP4: Its Implication for Atherosclerosis

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