Impairment of mucosal immunity by parenteral nutrition: Depressed nasotracheal influenza-specific secretory IgA levels and transport in parenterally fed mice

Objective To examine the effects on mucosal selective transport of polymeric IgA (plgA) and the ability of exogenous plgA to provide protection despite altered mucosal transport. Summary Background Data Parenteral nutrition significantly impairs established antipseudomonal immunity and IgA-mediated antiviral immunity in association with gut-associated lymphoid tissue mass atrophy. Lack of enteral feeding also induces mucosal effects. Methods After immunization, nasotracheal levels of influenza-specific IgA were measured in cannulated mice randomized to chow feeding or parenteral nutrition, Nonimmune animals were randomized to chow or total parenteral nutrition, and after 5 days of diet were given a mixture of two antiinfluenza monoclonal antibodies, plgA and IgG. Four hours after injection, nasal washes were collected and influenza-specific antibody levels were determined by enzyme-linked immunosorbent assay to calculate the selective transport index of IgA relative to IgG. In the final experiment, immunized animals were randomized to chow or parenteral feeding, and after 5 days, parenterally fed animals received either normal mouse serum or antiviral plgA before viral challenge. Viral shedding was measured at 42 hours after challenge. Results Parenteral nutrition significantly reduced virus-specific IgA in nasotracheal washes. Parenteral nutrition depressed the selective transport index, demonstrating impaired mucosal transport of plgA. Parenterally fed animals given specific antiviral plgA but not normal mouse serum eliminated virus from the airway and regained mucosal protection, demonstrating adequate residual transport for immunity if adequate plgA is present. Conclusion Although both decreased IgA production due to gut-associated lymphoid tissue atrophy and impaired mucosal transport occur when enteral feeding is not provided, residual transport can provide antiviral protection if exogenous antiviral plgA is available. Production, rather than transport, may be the most important factor in maintaining established respiratory tract IgA-mediated immunity.