Antigen Presentation in Protein-Energy Malnutrition

Protein-energy malnutrition is associated with intrinsic defects in macrophage (MØ) microbicidal function, but effects on MØ-CD4+ cell interaction are unclear. This study examined the effect of protein-energy malnutrition on components of Ag presentation (AP) by peritoneal macrophages (PMØ) and splenocyte responses (MLR) in the naive (resident) and infected state (mycobacterium-BCG), and assessed the potential role of prostaglandin (PGE2) and L-arginine-derived nitric oxide (NO') as regulatory mechanisms in these immune interactions. Mice were randomized to receive either a control (24% casein, RD) or low-protein (2.5% casein, LPD) diets for 8 weeks. PMØ and splenocytes were harvested and AP function and MLR assessed ±NG-monomethyl-L-arginine (NMMA; competitive inhibitor of NO' synthesis) or indomethacin (PGE2 inhibitor). PMØ components of AP were evaluated, including phagocytic function, MHC-class II (Ia) expression, and interleukin-1 (IL-1) and interleukin-6 (IL-6) production. PGE2 production and NO' (measured as NO-2) synthesis were also assessed. AP and MLR were preserved in protein-energy malnutrition in both resident and activated states, BCG infection in RD was associated with PMØ activation as measured by increased O-2 and NO-2 release, but impaired AP and MLR responses. NMMA and indomethacin enhanced AP and MLR in RD groups only. Individual components of PMØ AP (phagocytosis, IL-1 and IL-6 production) were defective during protein-energy malnutrition, as were NO-2 and PGE2 production. Thus, AP and MLR were preserved in LPD groups which may be related to a loss of prostaglandin- and L-arginine-mediated suppressor mechanisms.