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Immunological responses against Salmonella enterica serovar Typhimurium Braun lipoprotein and lipid A mutant strains in Swiss-Webster mice: potential use as live-attenuated vaccines.
Microb Pathog. 2008 Mar; 44(3):224-37.MP

Abstract

We generated and characterized Salmonella enterica serovar Typhimurium mutants that were deleted for the genes encoding Braun lipoprotein (lpp) alone or in conjunction with the msbB gene, which codes for an enzyme required for the acylation of the lipid A moiety of lipopolysaccharide. Two copies of the lpp gene, designated as lppA and lppB, exist on the chromosome of S. Typhimurium. These mutants were highly attenuated in a mouse infection model and induced minimal histopathological changes in mouse organs compared to those seen in infection with wild-type (WT) S. Typhimurium. The lppB/msbB and the lppAB/msbB mutants were maximally attenuated, and hence further examined in this study for their ability to induce humoral and cellular immune responses. Importantly, infection of out-bred Swiss-Webster mice with the mutant S. Typhimurium generated superior T helper cell type 2 (Th2) responses compared to WT S. Typhimurium, as determined by measuring IgG subclasses and cytokines. WT S. Typhimurium induced higher levels of IgG2a in sera of infected mice, while the lppB/msbB and lppAB/msbB mutants mounted higher levels of IgG1 as determined by an enzyme-linked immunosorbent assay. Mice immunized with lppB/msbB and lppAB/msbB mutants rapidly cleared WT S. Typhimurium upon subsequent rechallenge, and naïve mice passively immunized with sera from animals infected with S. Typhimurium mutants were protected against subsequent challenge with WT S. Typhimurium. Splenic T cells produced higher levels of interferon-gamma following ex vivo exposure to WT S. Typhimurium, while splenic T cells infected with the above-mentioned two mutants evoked higher levels of interleukin-6. Further, mice infected with lppB/msbB and lppAB/msbB mutants showed much higher levels of splenic T cell activation as measured by CD44(+) expression on CD4(+) T cells by flow cytometry and by incorporation of (3)H-thymidine compared to mice that were infected with WT S. Typhimurium. We expect the lppB/msbB and lppAB/msbB mutants to be excellent live-attenuated vaccine candidates, because they induced minimal inflammatory responses and evoked stronger and specific antibody and cellular immune responses.

Authors+Show Affiliations

Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 775551070, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17997275

Citation

Liu, Tie, et al. "Immunological Responses Against Salmonella Enterica Serovar Typhimurium Braun Lipoprotein and Lipid a Mutant Strains in Swiss-Webster Mice: Potential Use as Live-attenuated Vaccines." Microbial Pathogenesis, vol. 44, no. 3, 2008, pp. 224-37.
Liu T, König R, Sha J, et al. Immunological responses against Salmonella enterica serovar Typhimurium Braun lipoprotein and lipid A mutant strains in Swiss-Webster mice: potential use as live-attenuated vaccines. Microb Pathog. 2008;44(3):224-37.
Liu, T., König, R., Sha, J., Agar, S. L., Tseng, C. T., Klimpel, G. R., & Chopra, A. K. (2008). Immunological responses against Salmonella enterica serovar Typhimurium Braun lipoprotein and lipid A mutant strains in Swiss-Webster mice: potential use as live-attenuated vaccines. Microbial Pathogenesis, 44(3), 224-37.
Liu T, et al. Immunological Responses Against Salmonella Enterica Serovar Typhimurium Braun Lipoprotein and Lipid a Mutant Strains in Swiss-Webster Mice: Potential Use as Live-attenuated Vaccines. Microb Pathog. 2008;44(3):224-37. PubMed PMID: 17997275.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunological responses against Salmonella enterica serovar Typhimurium Braun lipoprotein and lipid A mutant strains in Swiss-Webster mice: potential use as live-attenuated vaccines. AU - Liu,Tie, AU - König,Rolf, AU - Sha,Jian, AU - Agar,Stacy L, AU - Tseng,Chien-Te K, AU - Klimpel,Gary R, AU - Chopra,Ashok K, Y1 - 2007/10/06/ PY - 2007/06/15/received PY - 2007/09/19/revised PY - 2007/09/21/accepted PY - 2007/11/13/pubmed PY - 2008/5/31/medline PY - 2007/11/13/entrez SP - 224 EP - 37 JF - Microbial pathogenesis JO - Microb Pathog VL - 44 IS - 3 N2 - We generated and characterized Salmonella enterica serovar Typhimurium mutants that were deleted for the genes encoding Braun lipoprotein (lpp) alone or in conjunction with the msbB gene, which codes for an enzyme required for the acylation of the lipid A moiety of lipopolysaccharide. Two copies of the lpp gene, designated as lppA and lppB, exist on the chromosome of S. Typhimurium. These mutants were highly attenuated in a mouse infection model and induced minimal histopathological changes in mouse organs compared to those seen in infection with wild-type (WT) S. Typhimurium. The lppB/msbB and the lppAB/msbB mutants were maximally attenuated, and hence further examined in this study for their ability to induce humoral and cellular immune responses. Importantly, infection of out-bred Swiss-Webster mice with the mutant S. Typhimurium generated superior T helper cell type 2 (Th2) responses compared to WT S. Typhimurium, as determined by measuring IgG subclasses and cytokines. WT S. Typhimurium induced higher levels of IgG2a in sera of infected mice, while the lppB/msbB and lppAB/msbB mutants mounted higher levels of IgG1 as determined by an enzyme-linked immunosorbent assay. Mice immunized with lppB/msbB and lppAB/msbB mutants rapidly cleared WT S. Typhimurium upon subsequent rechallenge, and naïve mice passively immunized with sera from animals infected with S. Typhimurium mutants were protected against subsequent challenge with WT S. Typhimurium. Splenic T cells produced higher levels of interferon-gamma following ex vivo exposure to WT S. Typhimurium, while splenic T cells infected with the above-mentioned two mutants evoked higher levels of interleukin-6. Further, mice infected with lppB/msbB and lppAB/msbB mutants showed much higher levels of splenic T cell activation as measured by CD44(+) expression on CD4(+) T cells by flow cytometry and by incorporation of (3)H-thymidine compared to mice that were infected with WT S. Typhimurium. We expect the lppB/msbB and lppAB/msbB mutants to be excellent live-attenuated vaccine candidates, because they induced minimal inflammatory responses and evoked stronger and specific antibody and cellular immune responses. SN - 0882-4010 UR - https://www.unboundmedicine.com/medline/citation/17997275/Immunological_responses_against_Salmonella_enterica_serovar_Typhimurium_Braun_lipoprotein_and_lipid_A_mutant_strains_in_Swiss_Webster_mice:_potential_use_as_live_attenuated_vaccines_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0882-4010(07)00134-9 DB - PRIME DP - Unbound Medicine ER -