Legionella pneumophila is an important cause of epidemic and sporadic human pneumonia. Intact recruited and immune inflammatory host defenses are essential for successful containment of this infection in man and animals. Critical interactions between cellular host defenses and Legionella can only be inferred, but not proven from study of clinical material. In vitro studies with human calls are, of necessity, limited by the selection of an artificial environment for culture. We have developed a model of Legionella pneumonia in rodents, which matches the human disease well. We have combined experiments performed in vitro and in vivo to supplement, rather than to supplant the studies that are being performed in other laboratories with human cells. The primary infection can be divided into phases: 1) initial unimpeded bacterial growth, 2) containment, and 3) clearance and resolution. A resident alveolar macrophage (AM) that is permissive for bacterial growth characterizes susceptible species and is probably necessary for productive infection. Neutrophils (PMNL), in contrast, provide the first protective defense against the bacteria. When examined in vitro phagocytes in the airspaces continue to support growth of Legionella during the phase of resolution (a time when specific immunological mechanisms have been activated), but they are less permissive than resident cells. We have demonstrated protection against rechallenge in animals that have survived prior sublethal infection. This protective effect can be reproduced partially by passive transfer of antibody into naive recipients. We propose studies to increase our understanding of immunological mechanisms in the successful containment of a primary infection and in acquired resistance to re-infection. We will characterize the humoral and cellular immune response in the Lewis rat and in Strain 2 guinea pigs. Subsequently, we will examine the effects of immunosuppression and reconstitution in animals that demonstrate innate or acquired resistance. We will explore the role of the stimulated or activated macrophage in the resistance to reinfection. These studies will increase our knowledge of immunity to an important human pathogen, but will also add to our knowledge of host defenses against an important class of human pathogens, pathogenic intracellular bacteria.
| Davis, G S; Winn Jr, W C (1987) Legionnaires' disease: respiratory infections caused by Legionella bacteria. Clin Chest Med 8:419-39 |
| Elliott, J A; Winn Jr, W C (1986) Treatment of alveolar macrophages with cytochalasin D inhibits uptake and subsequent growth of Legionella pneumophila. Infect Immun 51:31-6 |
