Lack of Bactericidal Effect of Mouse Serum on a Number of Common Microorganisms

Marcus, Stanley; Esplin, Don W.; Donaldson, David M.

doi:10.1126/science.119.3103.877

Cited by 52 publications

(27 citation statements)

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“…This could occur if the Ab is unable to facilitate the deposition of complement membrane attack complex at the Salmonella outer membrane. Alternatively, mouse complement per se may lack the necessary bactericidal activity to kill Salmonella, as suggested by early experiments on mouse complement (22,23).…”

Section: Resultsmentioning

confidence: 99%

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Absent Bactericidal Activity of Mouse Serum against Invasive African Nontyphoidal Salmonella Results from Impaired Complement Function but Not a Lack of Antibody

Siggins

Cunningham

Marshall

et al. 2011

The Journal of Immunology

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Nontyphoidal strains of Salmonella are a major cause of fatal bacteremia in Africa. Developing a vaccine requires an improved understanding of the relevant mechanisms of protective immunity, and the mouse model of Salmonella infection is useful for studying immunity to Salmonella in vivo. It is important to appreciate the similarities and differences between immunity to Salmonella in mice and men. Ab is important for protection against nontyphoidal Salmonella in both species, and we have previously found an important role for Ab in cell-free complement-mediated bactericidal activity against Salmonella in Africans. It is unclear whether this modality of immunity is relevant in the mouse model. C57BL/6, BALB/c, and C3H mice immunized with heat-killed Salmonella Typhimurium strains D23580 (African invasive strain) and SL1344 and live-attenuated strain SL3261 produced a Salmonella-specific Ab response. Sera from these mice deposited reduced levels of C3 on Salmonella compared with human sera and were unable to kill both wild-type and galE− rough mutant of D23580, indicating absent cell-free killing via classical and alternative complement pathways. Supplementing immune mouse sera with human complement enabled killing of Salmonella, whereas addition of human anti-Salmonella Ab to immune mouse sera had no effect. These findings indicate that mouse serum cannot effect cell-free complement-dependent killing of Salmonella, because of the reduced mouse complement ability to kill these bacteria compared with human complement. This difference in Ab-dependent immunity to Salmonella in mice and men must be considered when applying findings from the mouse model of Salmonella disease and vaccination response to man.

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Section: Resultsmentioning

confidence: 99%

“…Ab has previously been shown to have an important role in opsonizing Salmonella for phagocytosis and cellular killing in C57BL/6 mice (21). However, its ability to kill Salmonella using the cell-independent complement-mediated mechanism described in Africans is uncertain, particularly in view of the recognized limited activity of mouse complement (22,23).…”

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confidence: 99%

Absent Bactericidal Activity of Mouse Serum against Invasive African Nontyphoidal Salmonella Results from Impaired Complement Function but Not a Lack of Antibody

Siggins

Cunningham

Marshall

et al. 2011

The Journal of Immunology

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“…An important role for the opsonic mechanism is suggested by studies on murine salmonellosis. Although mouse complement has limited bactericidal activity (19,20), adoptive transfer studies (21,22) and studies in T cell-deficient mice (23,24) demonstrate the importance of antibody in immunity against Salmonella. Antibody is required for phagocytosis, oxidative burst function, and cellular killing of Salmonella by mouse macrophages (25).…”

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confidence: 99%

Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

Gondwe

Molyneux

Goodall

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

118

133

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Bacteremia caused by nontyphoidal strains of Salmonella is endemic among African children. Case-fatality rates are high and antibiotic resistance increasing, but no vaccine is currently available. T cells are important for clearance of Salmonella infection within macrophages, but in Africa, invasive Salmonella disease usually manifests in the blood and affects children between 4 months and 2 y of age, when anti- Salmonella antibody is absent. We have previously found a role for complement-fixing bactericidal antibody in protecting these children. Here we show that opsonic activity of antibody and complement is required for oxidative burst and killing of Salmonella by blood cells in Africans. Induction of neutrophil oxidative burst correlated with anti- Salmonella IgG and IgM titers and C3 deposition on bacteria and was significantly lower in African children younger than 2 y compared with older children. Preopsonizing Salmonella with immune serum overcame this deficit, indicating a requirement for antibody and/or complement. Using different opsonization procedures, both antibody and complement were found to be necessary for optimal oxidative burst, phagocytosis and killing of nontyphoidal Salmonella by peripheral blood cells in Africans. Although most strains of African nontyphoidal Salmonella can be killed with antibody and complement alone, phagocytes in the presence of specific antibody and complement can kill strains resistant to killing by immune serum. These findings increase the likelihood that an antibody-inducing vaccine will protect against invasive nontyphoidal Salmonella disease in African children.

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“…It is known that mouse serum is inadequate as a complement source and invariably reveals very low or undetectable activity in immune hemolysis or immune bactericidal tests. The lack or weakness of the complement activity in mouse sera has been attributed to deficiencies in various components of complement [2,3,6,8]. Shands et al [21] demonstrated that Porter's fragment 1 prepared from hyper-immune rabbit 1-globulin retained the capacity to cause the "clearance" phenomenon of S. typhimurium in mouse peritoneal cavity, though the fragment could not fix complement and failed to kill the bacteria in in vitro immune bactericidal reaction.…”

Section: Methodsmentioning

confidence: 99%

Antigenic Determinants of Salmonella for Production of “Clearance” Factor in Mouse Typhoid

Nakano

Saito

Toyasaki

1970

Japanese Journal of Microbiology

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The "clearance" factor produced in the peritoneal cavity of mice immunized with killed vaccines prepared from Salmonella typhimurium or S. enteritidis was identified as the specific antibodies elicited by the 0 side chain of the cell wall polysaccharides in the organisms used as immunogens. After immunization of mice with vaccines prepared from virulent Salmonella strains, complement-dependent antibacterial antibodies in the serum and "clearance" factors in the peritoneal cavity were found to appear coincidentally, to last for more than one year, and to have the same specificity against the virulent bacterial strains. The relationship between the complement-dependent antibacterial antibodies and "clearance" factor, and the mechanisms of bactericidal action of these antibacterial agents in experimental typhoid were discussed.

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Lack of Bactericidal Effect of Mouse Serum on a Number of Common Microorganisms

Cited by 52 publications

References 0 publications

Absent Bactericidal Activity of Mouse Serum against Invasive African Nontyphoidal Salmonella Results from Impaired Complement Function but Not a Lack of Antibody

Absent Bactericidal Activity of Mouse Serum against Invasive African Nontyphoidal Salmonella Results from Impaired Complement Function but Not a Lack of Antibody

Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans

Antigenic Determinants of Salmonella for Production of “Clearance” Factor in Mouse Typhoid

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