Abstract
Enhancing antiviral host defense responses through nutritional supplementation would be an attractive strategy in the fight against influenza. Using inoculation with live attenuated influenza virus (LAIV) as an infection model, we have recently shown that ingestion of sulforaphane-containing broccoli sprout homogenates (BSH) reduces markers of viral load in the nose. To investigate the systemic effects of short-term BSH supplementation in the context of LAIV-inoculation, we examined peripheral blood immune cell populations in non-smoking subjects from this study, with a particular focus on NK cells. We carried out a randomized, double-blinded, placebo-controlled study measuring the effects of BSH (N = 13) or placebo (alfalfa sprout homogenate, ASH; N = 16) on peripheral blood mononuclear cell responses to a standard nasal vaccine dose of LAIV in healthy volunteers. Blood was drawn prior to (day-1) and post (day2, day21) LAIV inoculation and analyzed for neutrophils, monocytes, macrophages, T cells, NKT cells, and NK cells. In addition, NK cells were enriched, stimulated, and assessed for surface markers, intracellular markers, and cytotoxic potential by flow cytometry. Overall, LAIV significantly reduced NKT (day2 and day21) and T cell (day2) populations. LAIV decreased NK cell CD56 and CD158b expression, while significantly increasing CD16 expression and cytotoxic potential (on day2). BSH supplementation further increased LAIV-induced granzyme B production (day2) in NK cells compared to ASH and in the BSH group granzyme B levels appeared to be negatively associated with influenza RNA levels in nasal lavage fluid cells. We conclude that nasal influenza infection may induce complex changes in peripheral blood NK cell activation, and that BSH increases virus-induced peripheral blood NK cell granzyme B production, an effect that may be important for enhanced antiviral defense responses.Trial Registration: ClinicalTrials.gov NCT01269723
Highlights
Enhancing antiviral host defense responses through nutritional supplementation would be an attractive strategy in the fight against influenza
We investigated the effects of short-term broccoli sprout homogenates (BSH) supplementation in the context of live attenuated influenza virus (LAIV) inoculation on peripheral blood immune cell populations, with a particular focus on natural killer (NK) cells, using blood samples from non-smokers in the randomized trial
Our results show an effect of intranasal LAIV on peripheral blood T cell and natural killer T (NKT) cell populations, and on peripheral blood NK cell surface marker expression and cytotoxic activity
Summary
Enhancing antiviral host defense responses through nutritional supplementation would be an attractive strategy in the fight against influenza. We have recently shown that short-term ingestion of broccoli sprout homogenates (BSH) reduces markers of viral replication in nasal lavage fluid cells after inoculation with the live attenuated influenza virus (LAIV) vaccine in smokers [1]. Previous studies have shown dose-dependent, short-term effects of BSH on the expression of Nrf2-dependent enzymes in the airways [4] and in the skin [5] of human volunteers. We have previously shown that ingestion of BSH in vivo, or supplementation of epithelial cells with SFN in vitro, enhances antiviral host defense responses [8,9,10]
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