Legionella pneumophila immunity and immunomodulation: nature and mechanisms.

ABSTRACT

L. pneumophila is a facultative intracellular opportunistic pathogen ubiquitously present in the environment. Much is now known concerning the ecological niche of this organism as well as many other characteristics of these bacteria, including physiology and biochemistry. However, much less is known about immune mechanisms responsible for host resistance vs susceptibility. Not only outer membrane protein rich fractions but also LPS-rich components are potent immunogens, both in experimental animals such as susceptible guinea pigs and more resistant rodent species like rats and mice. Immunity to these organisms can be readily observed by a variety of serologic techniques. Antibody titers increase rapidly after exposure of individuals to these bacteria either by infection or immunization. However, such antibody does not appear to play an important role in host resistance. Serum antibody plus complement is not lytic for the bacteria in vitro. Furthermore, antibody appears to promote the phagocytosis of the bacteria by monocytes and/or macrophages in culture but such phagocytosis does not result in killing of the bacteria, merely an enhanced uptake and subsequent replication of the organisms. Studies on cellular immunity have focused attention on the role of T lymphocytes, monocytes and macrophages. In addition, cutaneous hypersensitivity is readily induced by infection or immunization of experimental animals with Legionella or antigenic components. In vitro correlates of hypersensitivity is also readily evident after infection or immunization. Although lymphoid cells from guinea pigs only show evidence of responsiveness to Legionella antigens by the lymphocyte blastogenic reaction after animals have been sensitized, peripheral blood monocytes from man as well as splenocytes from mice show evidence of responsiveness to Legionella even before known infection or sensitization. However, higher blastogenic responses become evident after sensitization or infection. In addition, interleukins, such as interleukin 1 and 2, as well as interferon and tumor necrotizing factor, appear in response to Legionella antigens and seem to play a role in resistance mechanisms. Cellular replication of Legionella in monocytes from man as well as macrophages from susceptible animals seems related to susceptibility or resistance to these organisms. Further analyses of the nature and mechanism of humoral vs cellular immune responses to Legionella antigens will provide valuable information about immunity and resistance to these intracellular pathogens in susceptible individuals.