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Allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection.

Feng Y, Zhu X, Wang Q, Jiang Y, Shang H, Cui L, Cao Y - Malar. J. (2012)

Bottom Line: This effect is at least partially due to improved host immune responses.The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice.In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.

ABSTRACT

Background: During malaria infection, multiple pro-inflammatory mediators including IFN-γ, TNF and nitric oxide (NO) play a crucial role in the protection against the parasites. Modulation of host immunity is an important strategy to improve the outcome of malaria infection. Allicin is the major biologically active component of garlic and shows anti-microbial activity. Allicin is also active against protozoan parasites including Plasmodium, which is thought to be mediated by inhibiting cysteine proteases. In this study, the immunomodulatory activities of allicin were assessed during acute malaria infection using a rodent malaria model Plasmodium yoelii 17XL.

Methods: To determine whether allicin modulates host immune responses against malaria infection, mice were treated with allicin after infection with P. yoelii 17XL. Mortality was checked daily and parasitaemia was determined every other day. Pro-inflammatory mediators and IL-4 were quantified by ELISA, while NO level was determined by the Griess method. The populations of dendritic cells (DCs), macrophages, CD4+ T and regulatory T cells (Treg) were assessed by FACS.

Results: Allicin reduced parasitaemia and prolonged survival of the host in a dose-dependent manner. This effect is at least partially due to improved host immune responses. Results showed that allicin treatment enhanced the production of pro-inflammatory mediators such as IFN-γ, TNF, IL-12p70 and NO. The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10.

Conclusions: Allicin could partially protect host against P. yoelii 17XL through enhancement of the host innate and adaptive immune responses.

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Related in: MedlinePlus

Serum levels of pro-inflammatory cytokines IFN-γ and TNF. Sera were collected from allicin and PBS treated mice and the amounts of IFN-γ (A) and TNF (B) were assayed by ELISA on day 0, 3 and 5 PI. There was no significant difference among groups by Fisher’s LSD post-hoc test.
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Figure 2: Serum levels of pro-inflammatory cytokines IFN-γ and TNF. Sera were collected from allicin and PBS treated mice and the amounts of IFN-γ (A) and TNF (B) were assayed by ELISA on day 0, 3 and 5 PI. There was no significant difference among groups by Fisher’s LSD post-hoc test.

Mentions: As a cysteine protease inhibitor, the inhibitory effects of allicin on Plasmodium parasites were attributed to the direct action on parasites[30,32]. Because allicin also has immunomodulatory activity, whether improved disease outcomes by allicin treatments could result from strengthened host immunity against Plasmodium infection was investigated. Previous studies have shown that enhancement of Th1 responses during P. yoelii 17XL infection could reduce the initial parasite load and extend host survival time[43]. Here, the levels of several pro-inflammatory mediators in the sera of control and allicin-treated mice were evaluated. Allicin treatments increased IFN-γ levels on day 3 PI and treatment at 9 mg/kg increased TNF levels on both days 3 and 5 PI, although the differences were not statistically significant (Figure 2). To further investigate whether the elevated serum levels of pro-inflammatory cytokines were the result of increased production in splenocytes, the in vitro synthesis of IFN-γ, TNF, IL-12p70 and NO in cultured splenocytes from the control and allicin-treated mice were measured. Compared to the control, allicin treatments at both dosages caused significant increases in the production of IFN-γ and TNF by splenocytes on days 3 and 5 PI (P < 0.05) and the effect appeared to be dose-dependent (Figure 3A, B). More specifically, 9 mg/kg allicin treatment led to ~ seven times higher production of IFN-γ than 3 mg/kg allicin treatment on day 3 PI (Figure 3A). IFN-γ can promote the production of NO by macrophages to reduce the parasitaemia during P. yoelii 17XL infection. Therefore, NO production in cultured splenocytes, a hallmark of macrophage activation, was further studied. In support of earlier observation of other Th1 cytokines, both allicin treatment dosages increased NO production on days 3 and 5 PI (Figure 3C). Yet, the 3 mg/kg treatment group showed slight, insignificant increase of NO production as compared to control (Figure 3C, P > 0.05). Significant increase in NO2- was evident in the higher dose (9 mg/kg) of allicin treatment group (Figure 3C). IL-12 is an important stimulator of the T-cell response and plays a critical role in resistance to malaria[44-46]. Allicin treatments at both dosages caused increases in the production of IL-12p70 by splenocytes on days 3 and 5 PI and this effect also appeared to be dose-dependent, albeit the difference was not statistically significant (Figure 3D, P > 0.05). To evaluate whether allicin treatment affected Th2 immune response during the early stage of P. yoelii 17XL infection, the amount of IL-4 in the supernatant of cultured splenocytes was determined, and there was no significant difference between the experiment and control groups (Figure 3E, P > 0.05). Altogether, these results showed that allicin treatment preferentially promoted the production of pro-inflammatory mediators during acute malaria infection in a dose-dependent manner.


Allicin enhances host pro-inflammatory immune responses and protects against acute murine malaria infection.

Feng Y, Zhu X, Wang Q, Jiang Y, Shang H, Cui L, Cao Y - Malar. J. (2012)

Serum levels of pro-inflammatory cytokines IFN-γ and TNF. Sera were collected from allicin and PBS treated mice and the amounts of IFN-γ (A) and TNF (B) were assayed by ELISA on day 0, 3 and 5 PI. There was no significant difference among groups by Fisher’s LSD post-hoc test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472178&req=5

Figure 2: Serum levels of pro-inflammatory cytokines IFN-γ and TNF. Sera were collected from allicin and PBS treated mice and the amounts of IFN-γ (A) and TNF (B) were assayed by ELISA on day 0, 3 and 5 PI. There was no significant difference among groups by Fisher’s LSD post-hoc test.
Mentions: As a cysteine protease inhibitor, the inhibitory effects of allicin on Plasmodium parasites were attributed to the direct action on parasites[30,32]. Because allicin also has immunomodulatory activity, whether improved disease outcomes by allicin treatments could result from strengthened host immunity against Plasmodium infection was investigated. Previous studies have shown that enhancement of Th1 responses during P. yoelii 17XL infection could reduce the initial parasite load and extend host survival time[43]. Here, the levels of several pro-inflammatory mediators in the sera of control and allicin-treated mice were evaluated. Allicin treatments increased IFN-γ levels on day 3 PI and treatment at 9 mg/kg increased TNF levels on both days 3 and 5 PI, although the differences were not statistically significant (Figure 2). To further investigate whether the elevated serum levels of pro-inflammatory cytokines were the result of increased production in splenocytes, the in vitro synthesis of IFN-γ, TNF, IL-12p70 and NO in cultured splenocytes from the control and allicin-treated mice were measured. Compared to the control, allicin treatments at both dosages caused significant increases in the production of IFN-γ and TNF by splenocytes on days 3 and 5 PI (P < 0.05) and the effect appeared to be dose-dependent (Figure 3A, B). More specifically, 9 mg/kg allicin treatment led to ~ seven times higher production of IFN-γ than 3 mg/kg allicin treatment on day 3 PI (Figure 3A). IFN-γ can promote the production of NO by macrophages to reduce the parasitaemia during P. yoelii 17XL infection. Therefore, NO production in cultured splenocytes, a hallmark of macrophage activation, was further studied. In support of earlier observation of other Th1 cytokines, both allicin treatment dosages increased NO production on days 3 and 5 PI (Figure 3C). Yet, the 3 mg/kg treatment group showed slight, insignificant increase of NO production as compared to control (Figure 3C, P > 0.05). Significant increase in NO2- was evident in the higher dose (9 mg/kg) of allicin treatment group (Figure 3C). IL-12 is an important stimulator of the T-cell response and plays a critical role in resistance to malaria[44-46]. Allicin treatments at both dosages caused increases in the production of IL-12p70 by splenocytes on days 3 and 5 PI and this effect also appeared to be dose-dependent, albeit the difference was not statistically significant (Figure 3D, P > 0.05). To evaluate whether allicin treatment affected Th2 immune response during the early stage of P. yoelii 17XL infection, the amount of IL-4 in the supernatant of cultured splenocytes was determined, and there was no significant difference between the experiment and control groups (Figure 3E, P > 0.05). Altogether, these results showed that allicin treatment preferentially promoted the production of pro-inflammatory mediators during acute malaria infection in a dose-dependent manner.

Bottom Line: This effect is at least partially due to improved host immune responses.The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice.In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.

ABSTRACT

Background: During malaria infection, multiple pro-inflammatory mediators including IFN-γ, TNF and nitric oxide (NO) play a crucial role in the protection against the parasites. Modulation of host immunity is an important strategy to improve the outcome of malaria infection. Allicin is the major biologically active component of garlic and shows anti-microbial activity. Allicin is also active against protozoan parasites including Plasmodium, which is thought to be mediated by inhibiting cysteine proteases. In this study, the immunomodulatory activities of allicin were assessed during acute malaria infection using a rodent malaria model Plasmodium yoelii 17XL.

Methods: To determine whether allicin modulates host immune responses against malaria infection, mice were treated with allicin after infection with P. yoelii 17XL. Mortality was checked daily and parasitaemia was determined every other day. Pro-inflammatory mediators and IL-4 were quantified by ELISA, while NO level was determined by the Griess method. The populations of dendritic cells (DCs), macrophages, CD4+ T and regulatory T cells (Treg) were assessed by FACS.

Results: Allicin reduced parasitaemia and prolonged survival of the host in a dose-dependent manner. This effect is at least partially due to improved host immune responses. Results showed that allicin treatment enhanced the production of pro-inflammatory mediators such as IFN-γ, TNF, IL-12p70 and NO. The absolute numbers of CD4+ T cells, DCs and macrophages were significantly higher in allicin-treated mice. In addition, allicin promoted the maturation of CD11c+ DCs, whereas it did not cause major changes in IL-4 and the level of anti-inflammatory cytokine IL-10.

Conclusions: Allicin could partially protect host against P. yoelii 17XL through enhancement of the host innate and adaptive immune responses.

Show MeSH
Related in: MedlinePlus