The contribution of specific humoral or cellular immune response mechanisms to recovery from infection with Legionella Pneumophila, a newly recognized bacterium associated with pneumonia, is not fully understood. Cell mediated immune responses to legionellae are quite important in resistance and recovery from infection. Studies in this laboratory have indicated that L. pneumophila antigens are marked stimulators of enhanced antibody resposnes (i.e., highly adjuvantic) and also stimulate marked cell mediated immune responses as evidenced by positive skin reactivity and in vitro blastogenic responses and migration inhibitory factor formation by lymphoid cells from sensitized or infected animals. Preliminary studies have indicated that L. pneumophila antigens stimulate the formation or release of interleukins (IL-1 and IL-2), as well as interferons, especially gamma interferon. The general goal of this study is to examine in detail the role of Interleukin 1 repsonses to Legionella antigens. Studies are to be performed to determine the effects of L. pneumophila, either living organisms or formalin killed vaccine, as well as subcellular products thereof, such as purified lipopolysaccharide derivatives, in regards to their ability to stimulate IL-1 by host lymphoid cells. The cellular source of these factors will be determined by appropriate cell separation and isolation procedures for phagocytic cells from lymphoid cell populations. Studies will also be performed to monitor various lymphoid cell populations at various times after injection with L. pneumophila in regards to their ability to produce IL-1 utilizing various Legionella antigens to stimulate lymphoid cells in vitro. The presence of IL-1 in fluids obtained in vivo (i.e., peritoneal or pulmonary lavage and serum) will be determined at various times after infection, correlating their presence or absence with the course of infection. Finally, studies will be performed to determine the effects of passive administration of purified IL-1 on the course of infection with viable L. pneumophila using either normal mice or cyclophosphamide immunosuppressed animals. These studies will provide new information concerning the relationship of IL-1 formation in response to legionella immunization or infection.
| Widen, R H; Newton, C A; Klein, T W et al. (1993) Antibody-mediated enhancement of Legionella pneumophila-induced interleukin 1 activity. Infect Immun 61:4027-32 |
| Widen, R H; Klein, T W; Newton, C A et al. (1989) Induction of interleukin 1 by Legionella pneumophila in murine peritoneal macrophage cultures. Proc Soc Exp Biol Med 191:304-8 |
