Polysaccharides Isolated from Açaí Fruit Induce Innate Immune Responses

The Açaí (Acai) fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease

Nasal Acai Polysaccharides Potentiate Innate Immunity to Protect against Pulmonary Francisella tularensis and Burkholderia pseudomallei Infections

Pulmonary Francisella tularensis and Burkholderia pseudomallei infections are highly lethal in untreated patients, and current antibiotic regimens are not always effective. Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic therapies. Several natural agonists were screened for their ability to enhance host resistance to infection, and polysaccharides derived from the Acai berry (Acai PS) were found to have potent abilities as an immunotherapeutic to treat F. tularensis and B. pseudomallei infections. In vitro, Acai PS impaired replication of Francisella in primary human macrophages co-cultured with autologous NK cells via augmentation of NK cell IFN-γ. Furthermore, Acai PS administered nasally before or after infection protected mice against type A F. tularensis aerosol challenge with survival rates up to 80%, and protection was still observed, albeit reduced, when mice were treated two days post-infection. Nasal Acai PS administration augmented intracellular expression of IFN-γ by NK cells in the lungs of F. tularensis-infected mice, and neutralization of IFN-γ ablated the protective effect of Acai PS. Likewise, nasal Acai PS treatment conferred protection against pulmonary infection with B. pseudomallei strain 1026b. Acai PS dramatically reduced the replication of B. pseudomallei in the lung and blocked bacterial dissemination to the spleen and liver. Nasal administration of Acai PS enhanced IFN-γ responses by NK and γδ T cells in the lungs, while neutralization of IFN-γ totally abrogated the protective effect of Acai PS against pulmonary B. pseudomallei infection. Collectively, these results demonstrate Acai PS is a potent innate immune agonist that can resolve F. tularensis and B. pseudomallei infections, suggesting this innate immune agonist has broad-spectrum activity against virulent intracellular pathogens

Acai PS requires IFN-γ and NK cells for optimum protection against <i>B. pseudomallei</i> infection.

<p>Two days prior to infection, C57BL/6 mice received rat IgG, anti-IFN-γ, or anti-NK1.1 mAb. Mice were treated i.n. with PBS (n = 5–10/group) or 1 mg of Acai PS (n = 10/group) one day prior to i.n. infection with 1×10⁴ CFUs of <i>B. pseudomallei</i> 1026b. Survival was monitored over time. *P<0.05 as compared to animals receiving PBS and IgG. ∧P<0.05 as compared to animals receiving Acai PS and anti-IFN-γ.</p

Acai PS induces TNF-α and NO in type A <i>F. tularensis</i>-infected RAW264.7 cells, but not in murine BMDMs.

<p>Cells were treated and infected as in <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1002587#ppat-1002587-t001" target="_blank">Table 1</a>. 3/wells treatment at 20 hr post-infection shown; standard deviation in parentheses; results are representative of two independent experiments.</p>a<p>Mean NO (µM) or</p>b<p>TNF-α (ng/ml) production.</p>*<p>p<0.05 as compared to the same cell type not treated with Acai PS.</p>∧<p>p<0.05 as compared to the same cell type, with the same Acai treatment, treated with L-NMA at 20 hr post-infection. ND = not done.</p

Acai PS enhances the clearance of type A <i>F. tularensis</i> from RAW264.7 cells, but not murine BMDMs via NO.

<p>Cells were treated with Acai PS 16 hr prior to infection <i>F. tularensis</i> SchuS4 (MOI∼30), some wells were also pre-treated with 400 µM L-NMA.</p>a<p>Log₁₀ CFU/well from three wells/treatment shown; standard deviation in parentheses; results are representative of two independent experiments.</p>*<p>p<0.05 as compared to the same cell type not treated with Acai PS at the same time point.</p>∧<p>p<0.05 as compared to the same cell type, with the same Acai treatment, treated with L-NMA at 20 hr post-infection. ND = Not done.</p