Publication
Subversion of innate and adaptive immune activation induced by structurally modified lipopolysaccharide from Salmonella typhimurium
Journal Paper/Review - Jun 2, 2011
Pastelin-Palacios Rodolfo, Isibasi Armando, Gunn John S, Bonifaz Laura, Alpuche-Aranda Celia, Becker Ingeborg, García-Zepeda Eduardo A, Cunningham Adam F, Ludewig Burkhard, Arriaga-Pizano Lourdes, Cervantes-Barragan Luisa, Moreno-Eutimio Mario A, Pérez Shibayama Christian Ivan, Gil Cruz Cristina, López-Macías Constantino
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Pages
Brief description/objective
Salmonella are successful pathogens that infect millions of people every year. During infection, Salmonella typhimurium changes the structure of its lipopolysaccharide (LPS) in response to the host environment, rendering bacteria resistant to cationic peptide lysis in vitro. However, the role of these structural changes in LPS as in vivo virulence factors and their effects on immune responses and the generation of immunity are largely unknown. We report that modified LPS are less efficient than wild-type LPS at inducing pro-inflammatory responses. The impact of this LPS-mediated subversion of innate immune responses was demonstrated by increased mortality in mice infected with a non-lethal dose of an attenuated S. typhimurium strain mixed with the modified LPS moieties. Up-regulation of co-stimulatory molecules on antigen-presenting cells and CD4(+) T-cell activation were affected by these modified LPS. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing specific antibody responses. Immunization with modified LPS moiety preparations combined with experimental antigens, induced an impaired Toll-like receptor 4-mediated adjuvant effect. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing immunity against challenge with virulent S. typhimurium. Hence, changes in S. typhimurium LPS structure impact not only on innate immune responses but also on both humoral and cellular adaptive immune responses.