Pulmonary immunity to Listeria is enhanced by elimination of alveolar macrophages

To determine how resident alveolar macrophages (AM) regulate the antigen-pr esenting-cell (APC) activities of pulmonary dendritic cells (DC) in the res ponse to particulate antigen, we pretreated Lewis rats intratracheally with liposomes containing clodronate (LIP-CLOD), which eliminated AM in vivo. C ontrols received saline encapsulated in liposomes (LIP-SAL) or saline alone intratracheally. At Day 3, rats were injected intratracheally with 1 x 10( 7) heat-killed Listeria (HKL) and DC purified from lung were examined for t heir ability to stimulate HKL-immune T cells without added HKL. Only DC fro m LIP-CLOD-treated rats displayed enhanced APC activities for HKL. A second intratracheal HKL challenge at Day 14 yielded lymphocytic cuffing of the m icrovasculature in LIP-CLOD-treated lungs only. Intratracheal adoptive tran sfer of normal syngeneic AM into LIP-CLOD-treated rats suppressed APC activ ities of DC in vitro and the lymphocytic response in vivo. Bronchoalveolar macrophages from rats treated with LIP-CLOD and HKL showed decreased produc tion of nitric oxide (NO), a potent suppressor of DC and T-helper 1 lymphoc yte activities as compared with those of controls. We conclude that elimina ting AM in vivo reduces local production of NO and promotes pulmonary cell- mediated immunity to HKL.