Abstract
BackgroundVibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induce inflammation and septic shock. Mesenchymal stem cells (MSCs) are currently used to treat infectious and inflammatory diseases. Therefore, this study aimed to evaluate the immune-modulating effects of the LPS‐MSC‐conditioned medium (CM) on V. cholerae LPS immunization in a murine model.MethodsAfter preconditioning MSCs with LPS, mice were immunized intraperitoneally on days 0 and 14 with the following combinations: LPS + LPS-MSC-CM; detoxified LPS (DLPS) + MSC-CM; LPS + MSC sup; LPS; LPS-MSC-CM; MSC supernatant (MSC sup); and PBS. The mouse serum and saliva samples were collected to evaluate antibody (serum IgG and saliva IgA) and cytokine responses (TNF-α, IL-10, IL-6, TGF-β, IL-4, IL-5, and B-cell activating factor (BAFF)).ResultsThe LPS + LPS-MSC-CM significantly increased total IgG and IgA compared to other combinations (P < 0.001). TNF-α levels, in contrast to IL-10 and TGF-β, were reduced significantly in mice receiving the LPS + LPS-MSC-CM compared to mice receiving only LPS. IL-4, IL-5, and BAFF levels significantly increased in mice receiving increased doses of LPS + LPS-MSC-CM compared to those who received only LPS. The highest vibriocidal antibody titer (1:64) was observed in LPS + LPS-MSC-CM-immunized mice and resulted in a significant improvement in survival in infant mice infected by V. cholerae O1.ConclusionsThe LPS-MSC-CM modulates the immune response to V. cholerae LPS by regulating inflammatory and anti-inflammatory responses and inducing vibriocidal antibodies, which protect neonate mice against V. cholerae infection.
Highlights
Cholera, which is caused by Vibrio cholerae, is endemic in many regions of the world [1, 2]
The amount of anti-inflammatory cytokines decreased with reducing levels of inflammatory cytokines in the LPS-Mesenchymal stem cells (MSCs)‐conditioned medium (CM) over time (Fig. 2C, D)
LPS + LPS‐MSC‐CM immunization modulates inflammatory and anti‐inflammatory responses To study the immunomodulatory effects of the LPS + LPS‐MSC‐CM vaccine on inflammatory and antiinflammatory cytokines, 24 h after each immunization, we evaluated serum TNF-α, IL-6, and IL-10 levels in immunized and nonimmunized mice
Summary
Cholera, which is caused by Vibrio cholerae, is endemic in many regions of the world [1, 2]. The WHO has prequalified three whole-cell killed oral cholera vaccines: Dukoral®, which can be given to all individuals older than 2 years, and ShancholTM and Euvichol®, which can be given to all individuals older than 1 year [5, 6]. These vaccines do not provide complete long-term protection and require two doses two weeks apart with a booster every 2 years. Vibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. This study aimed to evaluate the immune-modulating effects of the LPS‐MSC‐conditioned medium (CM) on V. cholerae LPS immunization in a murine model
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