Impairment of Mucosal Immunity by Parenteral Nutrition: Depressed Nasotracheal Influenza-Specific Secretory IgA Levels and Transport in Parenterally Fed Mice

Abstract

ObjectiveTo examine the effects on mucosal selective transport of polymeric IgA (pIgA) and the ability of exogenous pIgA to provide protection despite altered mucosal transport. Summary Background DataParenteral 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. MethodsAfter 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, pIgA 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 pIgA before viral challenge. Viral shedding was measured at 42 hours after challenge.

Parenteral Nutrition Induces Organ Specific Alterations in Polymeric Immunoglobulin Receptor Levels

“…Tissue homogenate IgA levels drop significantly in lung and nasal passages of PN-fed mice, but levels are maintained in the small intestine. PN-fed mice preserve pIgR expression in the nasal passage and seem to augment pIgR levels in the lung consistent with our observations that adequate residual transport is present in the upper respiratory tract when IgA is provided exogenously [25]. Our data implies that PN has less effect on respiratory transport (although we limited our measurement to only one component of transport) than on production.…”

“…Lumen lavage specimens quantify the levels of IgA secreted onto mucosal surfaces by the epithelial cells while tissue homogenate IgA reflects IgA available for transport by pIgR, and pIgR protein levels measure an important component of the transport process. IgA levels in lavage specimens from the nasal passages and intestine dropped significantly with PN compared to chow fed mice replicating prior observations in regard to this particular outcome [25,31] and assuring that the model functioned and reliably reproduced conditions to interpret the new findings. Uniquely, this work demonstrates organ specific effects of enteral stimulation -or lack of enteral stimulation -on tissue (not luminal) IgA levels and the critical IgA transport protein, pIgR.…”

“…The overall effect of these alterations reduce available IgA production (reduced T & B cells and Th2-type cytokines) and transport (lowered intestinal pIgR levels) to impair or eliminate established anti-viral and antibacterial defenses in our murine model [13,16]. In one previous experiment, however, we documented that respiratory protection against the A/PR8 (H1N1) influenza virus was preserved in PN-fed mice when influenza-specific monoclonal polymeric IgA was provided exogenously [25]. This suggested that airway transport was still adequate to provide protection if adequate IgA was provided and led to our hypothesis that PN induces unique tissue-specific effects on transport and production.…”

“…Each alteration would appear to negatively impact luminal IgA levels by reducing production capacity (reduced cell mass & altered cytokines) or transport (reduced pIgR) of IgA from the site of production. In a model of IgAmediated antiviral defense however, the capacity of IgA transport in the upper respiratory tract of PN fed animals appeared at least adequate to provide protection when exogenous viralspecific IgA was provided [25]. Therefore, we hypothesized that PN induces tissue specific pIgR (transport) protein alterations in the upper and lower respiratory tract and the intestine.…”

Impairment of Mucosal Immunity by Total Parenteral Nutrition: Requirement for IgA in Murine Nasotracheal Anti-Influenza Immunity

“…NW-specific IgA results are expressed as nanograms of specific IgA per 100 g of total nasal lavage protein. Our previously described polymeric IgA (pIgA) antiinfluenza mAb pool served as the IgA standard (27). The protein concentration of the nasal secretions was determined using a micro protein assay (Bio-Rad, Hercules, CA), and protein and specific IgA levels were normalized to 100 g of total protein/ml of lavage fluid.…”