Abstract
The interaction between alveolar macrophages and lymphocytes may alter the establishment of pulmonary infection with Myco-bacterium tuberculosis. Studies with a guinea pig model of pulmonary tuberculosis have demonstrated that chronic, moderate protein deficiency has a detrimental impact on disease resistance and cell-mediated immune responses, including mitogen and antigen-induced lympho-proliferation. Resident alveolar macrophages (AM) in humans and rodents suppress lymphoproliferation by producing inhibitors which include nitric oxide (NO). The effect of dietary protein deficiency on the interaction between guinea pig AM and concanavalin-A (ConA)-induced autologous splenocytes was quantified in co-culture. The AM of normally-nourished, high protein (HP) guinea pigs inhibited the ConA-in-duced proliferation of splenocytes at AM: splenocyte ratios of 1:4 or higher. However, the AM of malnourished, low protein (LP) guinea pigs inhibited the proliferation of splenocytes at AM: splenocyte ratios of 1:40 or greater. Catalase and indomethacin did not reverse the inhibitory effects of AM from either HP or LP animals, indicating that neither hydrogen peroxide (H2O2) nor prostaglandin E2 (PGE2), respectively, were the mediators of immunosuppression. The addition of a NO synthesis inhibitor, n-monomethyl L-arginine (NMMA), did not affect the suppression of lymphoproliferation by guinea pig AM. Non-inhibitory levels of normal AM infected with M. tuberculosis H37Rv suppressed the proliferation of splenocytes to Con A, while the proliferation of splenocytes from protein-deficient guinea pigs was not influenced by co-culture with inhibitory levels of infected AM. Thus, dietary protein deficiency enhances the suppressive activity of resident alveolar macrophages at least 10-fold in the guinea pig, and neither NO, H2O2 nor PGE2 appear to be the modulating factors. Infection of AM with virulent mycobacteria alters the interaction between AM and splenocytes of HP, but not LP, guinea pigs. The detrimental impact of protein malnutrition on cellular immunity and disease resistance in this guinea pig model of pulmonary tuberculosis may be mediated, in part, by dietary effects on the interaction between AM and lymphocytes.