Renegar K B, Johnson C D, Dewitt R C, King B K, Li J, Fukatsu K, Kudsk K A
Department of Surgery, University of Tennessee, Memphis, TN 38163, USA.
J Immunol. 2001 Jan 15;166(2):819-25. doi: 10.4049/jimmunol.166.2.819.
Secretory IgA (SIgA) is the primary mucosal Ig and has been shown to mediate nasotracheal (NT) mucosal immunity in normal immune BALB/c mice. This finding has been challenged by a report of NT immunity without IgA in knockout mice, suggesting that IgA may not be necessary for the protection of mucosal surfaces. Although other protective mechanisms may become active in the congenital absence of SIgA, these mechanisms are not the primary means of protection in normal mice. In this paper we show that feeding chemically defined total parenteral nutrition (TPN) to genetically normal, immune ICR mice by the i.v. route results in loss of nasal anti-influenza immunity and a significant drop in influenza-specific SIgA in the upper respiratory tract compared with chow-fed mice (p < 0.005), while the serum influenza-specific IgG titer is unaffected. Loss of upper respiratory tract mucosal immunity is not related to serum Ab, because 10 of 13 TPN-fed mice shed virus into their nasal secretions despite adequate serum anti-influenza IgG titers. The number of IgG Ab-secreting cells in the nasal passages and spleens of TPN-fed mice was unaffected, while both the number and the percentage of splenic IgA-secreting cells were decreased relative to those in chow-fed animals. The loss of immunity is due to the route of nutrition, not the composition of the diet, because TPN solution fed orally via gastrostomy instead of i.v. maintains NT anti-influenza mucosal immunity. We hypothesize that delivery of nutrition via the gut triggers the release of gastrointestinal neuropeptides necessary for maintenance of the mucosal immune system.
分泌型免疫球蛋白A（SIgA）是主要的黏膜免疫球蛋白，已被证明在正常免疫的BALB/c小鼠中介导鼻气管（NT）黏膜免疫。这一发现受到了一项关于基因敲除小鼠中无IgA时NT免疫的报告的挑战，这表明IgA可能不是保护黏膜表面所必需的。尽管在先天性缺乏SIgA时其他保护机制可能会变得活跃，但这些机制在正常小鼠中并非主要的保护手段。在本文中，我们表明，通过静脉途径给基因正常、免疫的ICR小鼠喂食化学定义的全胃肠外营养（TPN），与喂食普通饲料的小鼠相比，会导致鼻内抗流感免疫力丧失，上呼吸道中流感特异性SIgA显著下降（p < 0.005），而血清中流感特异性IgG滴度不受影响。上呼吸道黏膜免疫的丧失与血清抗体无关，因为13只喂食TPN的小鼠中有10只尽管血清抗流感IgG滴度足够，但仍将病毒排入鼻分泌物中。喂食TPN的小鼠鼻道和脾脏中分泌IgG抗体的细胞数量未受影响，而脾脏中分泌IgA的细胞数量和百分比相对于喂食普通饲料的动物均有所减少。免疫丧失是由于营养途径而非饮食成分，因为通过胃造口术经口而非静脉喂食TPN溶液可维持NT抗流感黏膜免疫。我们推测，通过肠道提供营养会触发维持黏膜免疫系统所需的胃肠神经肽的释放。
