Impairment of mucosal immunity by total parenteral nutrition: Requirement for IgA in murine nasotracheal anti-influenza immunity

Secretory IgA (SIgA) is the primary mucosal Ig and has been shown to mediat e nasotracheal (NT) mucosal immunity in normal immune BALB/c mice. This fin ding 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 mucos al surfaces. Although other protective mechanisms may become active in the congenital absence of SIgA, these mechanisms are not the primary means of p rotection in normal mice. In this paper we show that feeding chemically def ined total parenteral nutrition (TPN) to genetically normal, immune ICR mic e 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 t heir 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 spleni c 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 delive ry of nutrition via the gut triggers the release of gastrointestinal neurop eptides necessary for maintenance of the mucosal immune system.