The Antiviral Effects of Heat-Killed <i>Lactococcus lactis</i> Strain Plasma Against Dengue, Chikungunya, and Zika Viruses in Humans by Upregulating the IFN-α Signaling Pathway
The growing risk of contracting viral infections due to high-density populations and ecological disruptions, such as climate change and increased population mobility, has highlighted the necessity for effective antiviral treatment and preventive measures against Dengue virus (DENV), Chikungunya viru...
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2024-11-01
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| author | Zhao Xuan Low Osamu Kanauchi Vunjia Tiong Norhidayu Sahimin Rafidah Lani Ryohei Tsuji Sazaly AbuBakar Pouya Hassandarvish |
| author_facet | Zhao Xuan Low Osamu Kanauchi Vunjia Tiong Norhidayu Sahimin Rafidah Lani Ryohei Tsuji Sazaly AbuBakar Pouya Hassandarvish |
| author_sort | Zhao Xuan Low |
| collection | DOAJ |
| description | The growing risk of contracting viral infections due to high-density populations and ecological disruptions, such as climate change and increased population mobility, has highlighted the necessity for effective antiviral treatment and preventive measures against Dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, there has been increasing attention on the use of probiotics as a potential antiviral option to reduce virus infections. The present study aimed to assess the immunomodulatory effects of heat-killed <i>Lactococcus lactis</i> strain plasma (LC-Plasma) on peripheral blood mononuclear cells (PBMCs) and its subsequent antiviral response against DENV, CHIKV, and ZIKV. To evaluate the immunomodulatory effects of LC-Plasma on PBMCs isolated from healthy individuals, PBMCs were cultured at a density of 2 × 10<sup>5</sup> cells/well and stimulated with 10 µg/mL of LC-Plasma. LC-plasma-stimulated PBMCs demonstrated elevated interferon-alpha (IFN-α) production and cluster of differentiation 86 (CD86) and human leukocyte antigen-DR isotype (HLA-DR) upregulation, potentially linked to plasmacytoid dendritic cell (pDC) activation. The replication of DENV, CHIKV, and ZIKV was dose-dependently inhibited when Huh-7 cells were stimulated with LC-Plasma-stimulated PBMC supernatant (LCP Sup). IFN-stimulated gene (ISG) expression, including IFN-stimulated gene 15 (ISG15), IFN-stimulated exonuclease gene 20 (ISG20), IFN-induced transmembrane protein 1 (IFITM-1), myxovirus resistance protein A (MxA), and radical S-adenosyl methionine domain-containing protein 2 (RSAD2), was significantly upregulated in LCP Sup-stimulated Huh-7 cells. Findings from this study indicate that LC-Plasma has the potential to induce IFN-α production, leading to an enhancement in the expression of ISGs and contributing to a broad-spectrum antiviral response. Thus, LC-Plasma may serve as a rational adjunctive treatment to ameliorate viral diseases, warranting future clinical trials. |
| format | Article |
| id | doaj-art-b7d35e3fa67b418fbdd340fdd51ac5df |
| institution | OA Journals |
| issn | 2076-2607 |
| language | English |
| publishDate | 2024-11-01 |
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| series | Microorganisms |
| spelling | doaj-art-b7d35e3fa67b418fbdd340fdd51ac5df2025-08-20T01:53:54ZengMDPI AGMicroorganisms2076-26072024-11-011211230410.3390/microorganisms12112304The Antiviral Effects of Heat-Killed <i>Lactococcus lactis</i> Strain Plasma Against Dengue, Chikungunya, and Zika Viruses in Humans by Upregulating the IFN-α Signaling PathwayZhao Xuan Low0Osamu Kanauchi1Vunjia Tiong2Norhidayu Sahimin3Rafidah Lani4Ryohei Tsuji5Sazaly AbuBakar6Pouya Hassandarvish7Tropical Infectious Disease Research and Education Centre (TIDREC), Universiti Malaya, Kuala Lumpur 50603, MalaysiaTropical Infectious Disease Research and Education Centre (TIDREC), Universiti Malaya, Kuala Lumpur 50603, MalaysiaTropical Infectious Disease Research and Education Centre (TIDREC), Universiti Malaya, Kuala Lumpur 50603, MalaysiaTropical Infectious Disease Research and Education Centre (TIDREC), Universiti Malaya, Kuala Lumpur 50603, MalaysiaDepartment of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, MalaysiaInstitute of Health Sciences, Kirin Holdings Co., Ltd., 2-26-1, Muraoka-Higashi, Fujisawa 251-8555, Kanagawa, JapanTropical Infectious Disease Research and Education Centre (TIDREC), Universiti Malaya, Kuala Lumpur 50603, MalaysiaTropical Infectious Disease Research and Education Centre (TIDREC), Universiti Malaya, Kuala Lumpur 50603, MalaysiaThe growing risk of contracting viral infections due to high-density populations and ecological disruptions, such as climate change and increased population mobility, has highlighted the necessity for effective antiviral treatment and preventive measures against Dengue virus (DENV), Chikungunya virus (CHIKV), and Zika virus (ZIKV). Recently, there has been increasing attention on the use of probiotics as a potential antiviral option to reduce virus infections. The present study aimed to assess the immunomodulatory effects of heat-killed <i>Lactococcus lactis</i> strain plasma (LC-Plasma) on peripheral blood mononuclear cells (PBMCs) and its subsequent antiviral response against DENV, CHIKV, and ZIKV. To evaluate the immunomodulatory effects of LC-Plasma on PBMCs isolated from healthy individuals, PBMCs were cultured at a density of 2 × 10<sup>5</sup> cells/well and stimulated with 10 µg/mL of LC-Plasma. LC-plasma-stimulated PBMCs demonstrated elevated interferon-alpha (IFN-α) production and cluster of differentiation 86 (CD86) and human leukocyte antigen-DR isotype (HLA-DR) upregulation, potentially linked to plasmacytoid dendritic cell (pDC) activation. The replication of DENV, CHIKV, and ZIKV was dose-dependently inhibited when Huh-7 cells were stimulated with LC-Plasma-stimulated PBMC supernatant (LCP Sup). IFN-stimulated gene (ISG) expression, including IFN-stimulated gene 15 (ISG15), IFN-stimulated exonuclease gene 20 (ISG20), IFN-induced transmembrane protein 1 (IFITM-1), myxovirus resistance protein A (MxA), and radical S-adenosyl methionine domain-containing protein 2 (RSAD2), was significantly upregulated in LCP Sup-stimulated Huh-7 cells. Findings from this study indicate that LC-Plasma has the potential to induce IFN-α production, leading to an enhancement in the expression of ISGs and contributing to a broad-spectrum antiviral response. Thus, LC-Plasma may serve as a rational adjunctive treatment to ameliorate viral diseases, warranting future clinical trials.https://www.mdpi.com/2076-2607/12/11/2304LC-Plasmaantiviralarbovirusesinterferonprobiotics |
| spellingShingle | Zhao Xuan Low Osamu Kanauchi Vunjia Tiong Norhidayu Sahimin Rafidah Lani Ryohei Tsuji Sazaly AbuBakar Pouya Hassandarvish The Antiviral Effects of Heat-Killed <i>Lactococcus lactis</i> Strain Plasma Against Dengue, Chikungunya, and Zika Viruses in Humans by Upregulating the IFN-α Signaling Pathway Microorganisms LC-Plasma antiviral arboviruses interferon probiotics |
| title | The Antiviral Effects of Heat-Killed <i>Lactococcus lactis</i> Strain Plasma Against Dengue, Chikungunya, and Zika Viruses in Humans by Upregulating the IFN-α Signaling Pathway |
| title_full | The Antiviral Effects of Heat-Killed <i>Lactococcus lactis</i> Strain Plasma Against Dengue, Chikungunya, and Zika Viruses in Humans by Upregulating the IFN-α Signaling Pathway |
| title_fullStr | The Antiviral Effects of Heat-Killed <i>Lactococcus lactis</i> Strain Plasma Against Dengue, Chikungunya, and Zika Viruses in Humans by Upregulating the IFN-α Signaling Pathway |
| title_full_unstemmed | The Antiviral Effects of Heat-Killed <i>Lactococcus lactis</i> Strain Plasma Against Dengue, Chikungunya, and Zika Viruses in Humans by Upregulating the IFN-α Signaling Pathway |
| title_short | The Antiviral Effects of Heat-Killed <i>Lactococcus lactis</i> Strain Plasma Against Dengue, Chikungunya, and Zika Viruses in Humans by Upregulating the IFN-α Signaling Pathway |
| title_sort | antiviral effects of heat killed i lactococcus lactis i strain plasma against dengue chikungunya and zika viruses in humans by upregulating the ifn α signaling pathway |
| topic | LC-Plasma antiviral arboviruses interferon probiotics |
| url | https://www.mdpi.com/2076-2607/12/11/2304 |
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