Murine model for study of cell-mediated immunity: protection against death from fully virulent Francisella tularensis infection

Eigelsbach, Henry T.; Hunter, Donald; Janssen, Werner A.; Dangerfield, H G; Rabinowitz, Stanley G.

doi:10.1128/iai.12.5.999-1005.1975

Cited by 36 publications

(12 citation statements)

References 31 publications

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“…Limited requirement for CD4+ and ClD8+ T cells in immunity to reinfection with F. tularensis. It is known that mice that resolve a primary F. tularensis infection are able to resist a subsequent challenge inoculum that is lethal for naive mice (13,14,17,21,26). The expression of protective immunity to secondary infection with 3.5 x 106 CFU of F. tularensis LVS is shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

CD4+ and CD8+ T-cell-dependent and -independent host defense mechanisms can operate to control and resolve primary and secondary Francisella tularensis LVS infection in mice

1994

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Immunity to experimental infection with the facultative intracellular bacterium FranciseUla tularensis is generally considered an example of T-cell-mediated, macrophage-expressed immunity. However, the results of the present study indicate that T-cell-independent mechanisms are also important in anti-FranciseUla defense.They show that mice selectively depleted of CD4+, CD8+, or both T-cell populations by treatment with T-cell subset-specific monoclonal antibodies remained capable of controlling and partly resolving a primary sublethal FranciseUla infection. Similarly, it was found that FranciseUla-immune mice depleted of either or both subsets of T cells retain a high degree of acquired immunity to reinfection. Together, these findings imply that resistance to primary and secondary tularemia can be mediated by cells other than CD4+ and CD8+ T cells.

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Section: Resultsmentioning

confidence: 99%

CD4+ and CD8+ T-cell-dependent and -independent host defense mechanisms can operate to control and resolve primary and secondary Francisella tularensis LVS infection in mice

1994

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“…Passive transfer of immunity to lethal LVS infections with both serum and cells (Table 4) suggests that protective host responses to this vaccine strain during primary disease differ from those that influence resistance to the wild-type Francisella strain. In earlier studies that focused on LVS as a vaccine rather than a pathogen, only cells from vaccinated animals were capable of adoptively transferring immunity to virulent F. tularensis (7,21). Here we demonstrate that serum is quite effective in protecting mice from i.p.…”

Section: Discussionmentioning

confidence: 99%

“…In early studies with LVS, cells and serum from immune animals were transferred to nonimmune recipients to assess the role of each in protection against virulent F. tularensis challenge. These studies suggest that LVS-immune cells, not serum, mediate protective immunity against infections with wild-type Francisella strains (7,21). Two questions, however, remain unresolved: the cells involved in passive transfer of immunity to wild-type F. tularensis and the relative roles of antibody and cellular responses in primary infection with F. tularensis LVS.…”

mentioning

confidence: 91%

Live vaccine strain of Francisella tularensis: infection and immunity in mice

et al. 1991

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The live vaccine strain (LVS) ofFrancisella tularensis caused lethal disease in several mouse strains. Lethality depended upon the dose and route of inoculation. The lethal dose for 50% of the mice (LD50) in four of six mouse strains (A/J, BALB/cHSD, C3H/HeNHSD, and SWR/J) given an intraperitoneal (i.p.) inoculation was less than 10 CFU. For the other two strains tested, C3H/HeJ and C57BL/6J, the i.p. log LD5* was 1.5 and 2.7, respectively. Similar susceptibility was observed in mice inoculated by intravenous (i.v.) and intranasal (i.n.) routes: in all cases the LD50 was less than 1,000 CFU. Regardless of the inoculation route (i.p., i.v., or i.n.), bacteria were isolated from spleen, liver, and lungs within 3 days of introduction of bacteria; numbers of bacteria increased in these infected organs over 5 days. In contrast to the other routes of inoculation, mice injected with LVS intradermally (i.d.) survived infection: the LD50 of LVS by this route was much greater than 105 CFU. This difference in susceptibility was not due solely to local effects at the dermal site of inoculation, since bacteria were isolated from the spleen, liver, and lungs within 3 days by this route as well. The i.d.-infected mice were immune to an otherwise lethal i.p. challenge with as many as 104 CFU, and immunity could be transferred with either serum, whole spleen cells, or nonadherent spleen cells (but not Ig+ cells). A variety of infectious agents induce different disease syndromes depending on the route of entry. Francisella LVS infection in mice provides a model system for analysis of locally induced protective effector mechanisms.

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“…When seen in association with the strong immunogenicity of the 43K protein in humans, this makes the protein an attractive F. tularensis antigen for studies, for instance, to elucidate its potentiality as a component vaccine against tularemia. In this context, assessment of the propensity of the 43K protein to induce cellmediated immunity is particularly important (6,18,22).…”

Section: Discussionmentioning

confidence: 99%

Competitive enzyme immunoassay for antibodies to a 43,000-molecular-weight Francisella tularensis outer membrane protein for the diagnosis of tularemia

1989

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Antibodies against a 43,000-molecular-weight Francisella tularensis outer membrane (OM) protein (43K protein) were measured in paired serum specimens from 23 patients with tularemia and matched against antibodies in sera from 25 patients with nontularemic infectious diseases and from 25 blood donors. Antibodies were measured by a competition enzyme-linked immunosorbent assay which tested the ability of human serum to compete with rabbit anti-43K protein antibodies for its binding to the F. tularensis OM coat. The sera from nontularemic patients and from blood donors, in dilutions of 1:16 and 1:64, respectively, showed no or very low levels of antibodies. All of the tularemia patients showed positive tests with the first, the second, or both of the serum specimens examined. For instance, with serum diluted 1:64, each of the serum specimens showed a sensitivity of 95.7% and a specificity of 96%. When used for antibody competition in Western blotting (immunoblotting), the rabbit anti-43K selectively blocked the binding of human serum antibodies to the 43,000-molecular-weight protein. This protein was immunoaccessible in Formalin-killed F. tularensis. These data indicate an important role of the 43,000-molecular-weight OM protein in the immunobiology of tularemia and emphasize its potential usefulness as an antigen in serodiagnostic tests.

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Murine model for study of cell-mediated immunity: protection against death from fully virulent Francisella tularensis infection

Cited by 36 publications

References 31 publications

CD4+ and CD8+ T-cell-dependent and -independent host defense mechanisms can operate to control and resolve primary and secondary Francisella tularensis LVS infection in mice

CD4+ and CD8+ T-cell-dependent and -independent host defense mechanisms can operate to control and resolve primary and secondary Francisella tularensis LVS infection in mice

Live vaccine strain of Francisella tularensis: infection and immunity in mice

Competitive enzyme immunoassay for antibodies to a 43,000-molecular-weight Francisella tularensis outer membrane protein for the diagnosis of tularemia

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