title: Impairment of mucosal immunity by total parenteral nutrition: requirement for IgA in murine nasotracheal anti-influenza immunity.
abstract: 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.
authors.affiliation: Department of Surgery, University of Tennessee, Memphis, TN 38163, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Renegar
authors.forename: C D
authors.initials: CD
authors.lastname: Johnson
authors.forename: R C
authors.initials: RC
authors.lastname: Dewitt
authors.forename: B K
authors.initials: BK
authors.lastname: King
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Fukatsu
authors.forename: K A
authors.initials: KA
authors.lastname: Kudsk
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000502:physiology*; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D009980:Influenza A virus / Q000276:immunology*; D007262:Infusions, Intravenous / Q000009:adverse effects; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017817:Nasal Lavage Fluid / Q000276:immunology; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D014132:Trachea / Q000276:immunology / Q000378:metabolism
chemical_list: D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory