Sains Malaysiana 48(10)(2019): 2249–2256

http://dx.doi.org/10.17576/jsm-2019-4810-21

Role of Different Salmonella enterica Serotypes in THP-1 Macrophage-Derived Foam Cell Autophagy and Inflammatory Response

(Peranan Serotip Berbeza Salmonella enterica pada Tindak Balas Sel Buih THP-1 Makrofaj Terbitan Autofagi dan Inflamasi)

MIN YI WONG¹, YUAN-HSI TSENG¹, TSUNG-YU HUANG², CHENG-HSUN CHIU^3,4, CHYI-LIANG CHEN³ & YAO-KUANG HUANG¹*

¹Division of Thoracic and Cardiovascular Surgery, Chiayi Chang Gung Memorial Hospital, Puzi City, Chiayi County 613, and College of Medicine, Chang Gung University, Taoyuan City 333, Taiwan (R.O.C.)

²Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan City 333, Taiwan (R.O.C.)

³Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan City 333, Taiwan (R.O.C.)

⁴Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Children’s Hospital and Chang Gung University, Taoyuan City 333, Taiwan (R.O.C.)

Diserahkan: 22 Januari 2019/Diterima: 12 September 2019

ABSTRACT

Infected aortic aneurysm is a rare but life-threatening condition. Intimal injury, especially in arteries with atherosclerotic plaques, is vulnerable to Salmonella species. In this study, THP-1 macrophage-derived foam cells were used to mimic the atherosclerotic plaques. We investigated the role of different Salmonella serotype infections in foam cell autophagy and inflammatory response. Three different serotypes of Salmonella enterica-Typhimurium, Enteritidis, and Choleraesuis - with or without a virulence plasmid were used in this study. The foam cell model was established and observed under confocal microscopy. The expression of autophagy and inflammasome-related proteins after Salmonella infection was detected by Western blotting, and the secretion of the proinflammatory cytokines interleukin-1β and IL-18 was detected using ELISA. The plasmid-bearing S. enteritidis OU7130- and plasmid-less S. choleraesuis OU7266-infected foam cells both showed a lower expression of beclin-1 at 0.5 h post-infection (hpi) and p62 at 2 hpi as well as a higher expression of caspase-1 at 2 hpi than other infected cells. Moreover, infection of OU7266 induced the highest IL-1β and IL-18 production among the tested strains. In conclusion, the virulence plasmid of S. enteritidis OU7130 induced foam cell inflammatory responses, whereas that of S. choleraesuis played an opposite role. The different serotype of Salmonella may impact the infected aortic aneurysms through regulating inflammatory balance of the macrophage and foam cells in the atherosclerotic plaque.

Keywords: Autophagy; foam cells; Salmonella serotypes; virulence plasmid

ABSTRAK

Aneurisma aortik yang terjangkit adalah keadaan yang jarang berlaku namun boleh mengancam nyawa. Kecederaan intimal, terutamanya dalam arteri dengan plak atherosklerosis, terdedah kepada spesies Salmonella. Dalam kajian ini, sel buih yang berasal daripada makrofaj THP-1 digunakan untuk meniru plak aterosklerotik. Kami mengkaji peranan jangkitan serotip Salmonella yang berbeza dalam autophagia sel buih dan tindak balas keradangan. Tiga serotip Salmonella enterica - Typhimurium, Enteritidis dan Choleraesuis-dengan atau tanpa kevirulenan plasmid digunakan dalam kajian ini. Model sel buih telah ditubuhkan dan diperhatikan di bawah mikroskopi konflik. Ekspresi protein yang berkaitan dengan autofagia dan inflamasom selepas jangkitan Salmonella dikesan oleh blot Western, dan rembesan sitokin proinflamasi interleukin-1β dan IL-18 dikesan menggunakan ELISA. Pembekuan plasmid S. enteritidis OU7130- dan sel-sel buih yang dioksida S. choleraesuis OU7266 kedua-duanya menunjukkan ungkapan beclin-1 yang lebih rendah pada 0.5 jam selepas jangkitan (hpi) dan p62 pada 2 hpi serta ungkapan kaspase-1 yang lebih tinggi pada 2 hpi daripada sel yang dijangkiti yang lain. Tambahan pula, jangkitan OU7266 mendorong kepada pengeluaran tertinggi IL-1β dan IL-18 dalam kalangan strain yang diuji. Sebagai kesimpulan, plasmid virulensi S. enteritidis OU7130 bertindak balas dengan keradangan sel busa, sedangkan S. choleraesuis memainkan peranan yang bertentangan. Serotip Salmonella yang berlainan boleh memberi kesan kepada aneurisma aortik yang dijangkiti melalui mengawal keseimbangan radang makrofaj dan buih di plak aterosklerotik.

Kata kunci: Autofagi; kevirulenan plasmid; sel buih; serotip Salmonella

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*Pengarang untuk surat-menyurat; email: yaokuang@gmail.com