Mechanism of the protective immunity against murine typhoid: persistence of salmonella L forms in the liver after immunization with live-cell vaccines

Abstract

Live‐cell vaccines of Salmonella typhimurium, either a sub‐lethal dose of a wild‐type (strain LT2) or a high dose of its two‐heptose Rd1 mutant (strain SL1004), induced acquired resistance to murine typhoid, which remained 180 days after immunozation. Growth of S. typhimurium as a bacillary form ceased between days 30 and 60 of immunization, but L forms of this bacterium colonized the liver (the mean number of L forms in the liver: 600 L‐forming units) even at 180 days post‐immunization. In contrast, a high inoculum of either a Ra mutant (strain TV148) of strain LT2 or S. schottmülleri 8006 sharing the same O antigenic components with those of S. typhimurium induced only a short‐lived protection in proportion to the number of L forms in the liver, and the protective immunity was lost before day 180. However, there was no significant difference in the salmonella‐specific T‐cell responses among groups of immunized mice on day 180 of immunization. A lethal infection with strain LT2 in mice which had been immunized 75 days previously with living cells of strain SL1004 resulted in a rapid clearance of the challenge inoculum, together with a rapid elevation of anti‐S. typhimurium antibody responses. Thus, the present data suggest that the long‐lived immunity conferred upon live S. typhimurium vaccines is attributable to the colonization of this bacterium in the liver as L forms and the ability to colonize the liver as L forms is independent of the brain length of salmonella O‐antigens.

Host adapted serotypes of Salmonella enterica

“…Furthermore, Typhi induces ruffling and micropinocitosis in murine macrophages, but internalization is followed by formation of fewer numbers of SP than Typhimurium, an indicator of reduced capability to survive within macrophages that is essential in pathogenesis [201,202]. However, the exact role of the survival of salmonella in macrophages is not known and is made more difficult to rationalize by the reported ability of salmonella to lyse macrophages both in itro and in i o [203][204][205]. Recently a lack of correlation between the animal species from which macrophages were isolated and the ability of HA-serotypes and S. typhimurium to survive within these macrophages has been published.…”

Protective Capacity of L‐Form Salmonella typhimurium against Murine Typhoid in C3H/HeJ Mice

“…Thus, this mechanism should be elucidated to understand the mechanism of the long-lived immunity induced by either S. typhimurium or its L forms, since Salmonella L forms appeared in the liver of mice immunized with live-cell vaccines of S . typhimurium only after protective immunity was established (22).…”

“…However, the precise mechanisms underlying both the generation and nature of Salmonella-specific immunity remain undefined, since even nonviable vaccines, which induce only humoral immunity, can offer effective protection (1,11,13,15,21). Our previous study (22) showed that S. typhimurium survived in the reticuloendothelial system (RES) as an L form long after bacillary forms had been cleared from the RES. If L-form S. typhimurium can induce the long-lived immunity resulting from its persistence in the RES, our hypothesis (22) that the strains of S. typhimurium able to establish "an L-form carrier state" can confer the long-lasting immunity would be verified.…”

“…Our previous study (22) showed that S. typhimurium survived in the reticuloendothelial system (RES) as an L form long after bacillary forms had been cleared from the RES. If L-form S. typhimurium can induce the long-lived immunity resulting from its persistence in the RES, our hypothesis (22) that the strains of S. typhimurium able to establish "an L-form carrier state" can confer the long-lasting immunity would be verified.…”

The Polysaccharide Portion of Lipopolysaccharide Regulates Antigen-Specific T-Cell Activation via Effects on Macrophage-Mediated Antigen Processing

“…Based on colony morphology, mutant strains that have incomplete LPS molecules are termed rough while the wild type is termed smooth. Wild-type strains of S. typhimurium have a 50% lethal dose of Ͻ10 organisms in susceptible mice (11), while rough mutants are avirulent (50% lethal dose of Ն10 9 ) (30). All strains have a lipid A region and a minimum of two 2-keto-3-deoxyoctulosonic acid moieties (53).…”