Route of nutrition influences generation of antibody-forming cells and initial defense to an active viral infection in the upper respiratory tract

Abstract

Objective: To assess whether lack of enteral feeding significantly impairs generation of specific immune responses to an acute viral infection.

Summary background data: Parenteral feeding provides adequate nutrients to meet metabolic needs, but lack of enteral stimulation creates a defect in mucosal immunity characterized by loss of IgA-mediated defenses in the respiratory tract.

Methods: The enzyme-linked Immunospot (ELISPOT) assay was used to determine accumulation of immunologic cells in the nasal passages after diet manipulation. Viral shedding and nasal IgA levels were measured in additional groups of mice.

Results: After determining the time course of antibody-forming cells (AFCs) via ELISPOT to an active infection with the A/PR8 influenza virus, a significant reduction was found in total AFCs, IgA-producing AFCs, and IgG-producing AFCs over the course of a 13-day experiment with significant depression in viral-specific respiratory IgA levels. Eight days following an active infection, seven of nine total parenteral nutrition-fed animals continued to have viral shedding in the nasal passages compared to one of nine chow-fed mice and one of six animals fed a complex enteral diet.

Conclusions: Lack of enteral stimulation significantly impairs the generation of IgA-mediated mucosal immunity.

Figure 1. Timeline showing the number of AFCs (IgG-, IgA-, IgM-, and total Ab-producing cells) appearing after nasal inoculation with virus in nonimmune mice on days 3, 6, 10, 13, and 20.

Figure 2. Total IgM AFC numbers in nasal passages. Mice were inoculated with virus on day 0 and fed chow, CED, or IV-TPN for 6, 9, or 13 days. There was no statistically significant difference between groups at any time points.

Figure 3. Total IgA AFC numbers in nasal passages. Mice were inoculated with virus on day 0 and fed chow, CED, or IV-TPN for 6, 9, or 13 days. *P < .05 versus IV-TPN day 13; †P < .05 versus CED day 13; ¶P < .007 versus chow days 6 and 9; ‡P < .03 versus CED day 6.

Figure 4. Total IgG AFC numbers in nasal passages. Mice were inoculated with virus on day 0 and fed chow, CED, or IV-TPN for 6, 9, or 13 days. *P < .05 versus IV-TPN day 13; †P < .009 versus chow day 6; ¶P < .05 versus IV-TPN day 9; ‡P < .02 versus CED day 6.

Figure 5. Total number of AFCs (IgG, IgA, IgM) in nasal passages. Mice were inoculated with virus on day 0 and fed chow, CED, or IV-TPN for 6, 9, or 13 days. *P < .05 ver-sus IV-TPN day 13; †P < .02 versus chow days 6 and 9; ‡P 0.05 versus CED day 6.

Figure 6. Effect of route of nutrition on viral-specific respiratory IgA levels. Mice were nasally inoculated with virus 3 weeks before entry into the experimental protocol. After 5 days of feeding with chow, CED, or IV-TPN, viral-specific respiratory IgA levels were measured. *P < .003 versus chow; †P < .04 versus CED.

Figure 7. (A) Virus was cleared from the nasal passages of most animals by day 8. (B) Viral shedding at day 8 was significantly greater in IV-TPN-fed mice than chow-fed or CED-fed animals (P < .05).