Human milk oligosaccharides (HMO) contribute to innate immunity by enhancing growth of beneficial bacteria, epithelial cell maturation and mucosal barrier integrity. They have immunomodulatory effects and can block pa...Human milk oligosaccharides (HMO) contribute to innate immunity by enhancing growth of beneficial bacteria, epithelial cell maturation and mucosal barrier integrity. They have immunomodulatory effects and can block pathogen binding to host cell surface glycans or receptors. We investigated the effects of 2’-fucosyllactose (2’FL), 6’-sialyllactose (6’SL), 3’-sialyllactose (3’SL) and lacto-N-neoTetraose (LNnT) on human respiratory epithelial cell lines or peripheral blood mononuclear cells (PBMCs) following respiratory viral infectionin vitro. Expression of cytokines and viral load were monitored in infected cells. These biomarkers of innate immunity were selected since viral load and cytokine levels (IP-10, MIP-1α, IL-6, IL-8, TNF-α) have been correlated with disease severity in respiratory syncytial virus (RSV) and influenza (IAV) virus infectionin vivo. 2’FL significantly decreased RSV viral load and cytokines associated with disease severity (IL-6, IL-8, MIP-1α) and inflammation (TNF-α, MCP-1) in airway epithelial cells. LNnT and 6’SL significantly decreased IAV viral load in airway epithelial cells. 6’SL dose-dependently down-regulated IP-10 and TNF-α in RSV infected PBMCs. HMO at or below levels found in breast milk enhance innate immunity to respiratory viruses in vitro and may interact directly with cells to modulate biomarkers of innate immunity.展开更多
AIM: To test whether high-frequency electrical stimulation(HES) of the bilateral cervical vagus nerves reduces the airway responses to methacholine(MCh).METHODS: Guinea pigs were pretreated with saline(Sal, n = 9) or ...AIM: To test whether high-frequency electrical stimulation(HES) of the bilateral cervical vagus nerves reduces the airway responses to methacholine(MCh).METHODS: Guinea pigs were pretreated with saline(Sal, n = 9) or ovalbumin(Ova, n = 10) aerosol for two weeks(5 min/d, 5 d/wk) and subsequently anesthetized, paralyzed, tracheotomized and artificially ventilated. Both total lung resistance(RL) and dynamic pulmonary compliance(Cdyn) were recorded. In addition, the effects of vagal low-frequency electrical stimulation(LES, monophasic, 50 Hz) and HES(monophasic and biphasic, 1 and 2.5 kH z) for about 10 s or 2 min on the responses of RL and Cdyn to MCh aerosol-induced bronchoconstriction were compared in both groups of guinea pigs. In a few guinea pigs, the impact of bivagotomy on the RL responses to MCh was assessed.RESULTS: Before MCh challenge, LES, but not HES, significantly increased RL by about 30%(P < 0.01) and decreased Cdyn by about 20%(P < 0.01) similarly in both groups. MCh aerosol for 2 min elevated RL and diminished Cdyn more in Ova- than Sal-treated animals(RL: 313% ± 52% vs 113% ± 17%, P < 0.01; Cdyn:-56% ± 7% vs-21% ± 3%, P < 0.01). During MCh-induced airway constriction, LES further enhanced, but HES decreased RL and this decrease was greater in Ova-(about 45%) than Sal-treated animals(about 34%, P < 0.01) with little change in cardiovascular activity. On the other hand, LES further reduced whereas HES increased Cdyn more in Ova-(about 20%) than Sal-treated animals(about 13%, P < 0.01). In addition, bivagotomy almost eliminated the RL and Cdyn responses to MCh. CONCLUSION: We conclude that vagal HES is able to alleviate the bronchoconstriction induced by MCh in anesthetized guinea pigs, likely via reversible inhibition/blockade of vagal conduction.展开更多
文摘Human milk oligosaccharides (HMO) contribute to innate immunity by enhancing growth of beneficial bacteria, epithelial cell maturation and mucosal barrier integrity. They have immunomodulatory effects and can block pathogen binding to host cell surface glycans or receptors. We investigated the effects of 2’-fucosyllactose (2’FL), 6’-sialyllactose (6’SL), 3’-sialyllactose (3’SL) and lacto-N-neoTetraose (LNnT) on human respiratory epithelial cell lines or peripheral blood mononuclear cells (PBMCs) following respiratory viral infectionin vitro. Expression of cytokines and viral load were monitored in infected cells. These biomarkers of innate immunity were selected since viral load and cytokine levels (IP-10, MIP-1α, IL-6, IL-8, TNF-α) have been correlated with disease severity in respiratory syncytial virus (RSV) and influenza (IAV) virus infectionin vivo. 2’FL significantly decreased RSV viral load and cytokines associated with disease severity (IL-6, IL-8, MIP-1α) and inflammation (TNF-α, MCP-1) in airway epithelial cells. LNnT and 6’SL significantly decreased IAV viral load in airway epithelial cells. 6’SL dose-dependently down-regulated IP-10 and TNF-α in RSV infected PBMCs. HMO at or below levels found in breast milk enhance innate immunity to respiratory viruses in vitro and may interact directly with cells to modulate biomarkers of innate immunity.
基金Supported by RO1 HL107462 from the National Heart,Lung,and Blood Institute,Bethesda,MD,and Neuro Stimulation Techologies,Inc.Albuquerque,NM
文摘AIM: To test whether high-frequency electrical stimulation(HES) of the bilateral cervical vagus nerves reduces the airway responses to methacholine(MCh).METHODS: Guinea pigs were pretreated with saline(Sal, n = 9) or ovalbumin(Ova, n = 10) aerosol for two weeks(5 min/d, 5 d/wk) and subsequently anesthetized, paralyzed, tracheotomized and artificially ventilated. Both total lung resistance(RL) and dynamic pulmonary compliance(Cdyn) were recorded. In addition, the effects of vagal low-frequency electrical stimulation(LES, monophasic, 50 Hz) and HES(monophasic and biphasic, 1 and 2.5 kH z) for about 10 s or 2 min on the responses of RL and Cdyn to MCh aerosol-induced bronchoconstriction were compared in both groups of guinea pigs. In a few guinea pigs, the impact of bivagotomy on the RL responses to MCh was assessed.RESULTS: Before MCh challenge, LES, but not HES, significantly increased RL by about 30%(P < 0.01) and decreased Cdyn by about 20%(P < 0.01) similarly in both groups. MCh aerosol for 2 min elevated RL and diminished Cdyn more in Ova- than Sal-treated animals(RL: 313% ± 52% vs 113% ± 17%, P < 0.01; Cdyn:-56% ± 7% vs-21% ± 3%, P < 0.01). During MCh-induced airway constriction, LES further enhanced, but HES decreased RL and this decrease was greater in Ova-(about 45%) than Sal-treated animals(about 34%, P < 0.01) with little change in cardiovascular activity. On the other hand, LES further reduced whereas HES increased Cdyn more in Ova-(about 20%) than Sal-treated animals(about 13%, P < 0.01). In addition, bivagotomy almost eliminated the RL and Cdyn responses to MCh. CONCLUSION: We conclude that vagal HES is able to alleviate the bronchoconstriction induced by MCh in anesthetized guinea pigs, likely via reversible inhibition/blockade of vagal conduction.
