Immunity to Intracellular Salmonella Depends on Surface-associated Antigens

PLoS Pathogens

Konstantin Rizos¹  Anne K. Schemmer²  Somedutta Barat²  Beatrice Claudi²  Dirk Bumann²  Alain Mazé²  Neil Burton²  Dennis Kirchhoff³  Yvonne Willer⁴  Alexander Schmidt⁵ 

[1] Department of Molecular Biology, Max-Planck-Institute for Infection Biology, Berlin, Germany;Focal Area Infection Biology, Biozentrum, University of Basel, Basel, Switzerland;Immunomodulation Group, Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany;Junior Group “Mucosal Infections”, Hannover Medical School, Hannover, Germany;Proteomics Core Facility, Biozentrum, University of Basel, Basel, Switzerland

关键词: Salmonella;    Salmonellosis;    Antigens;    T helper cells;    Outer membrane proteins;    Antigen encapsulation;    Antigen processing;    recognition;    Immune response;   

DOI  :  10.1371/journal.ppat.1002966

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Invasive Salmonella infection is an important health problem that is worsening because of rising antimicrobial resistance and changing Salmonella serovar spectrum. Novel vaccines with broad serovar coverage are needed, but suitable protective antigens remain largely unknown. Here, we tested 37 broadly conserved Salmonella antigens in a mouse typhoid fever model, and identified antigen candidates that conferred partial protection against lethal disease. Antigen properties such as high in vivo abundance or immunodominance in convalescent individuals were not required for protectivity, but all promising antigen candidates were associated with the Salmonella surface. Surprisingly, this was not due to superior immunogenicity of surface antigens compared to internal antigens as had been suggested by previous studies and novel findings for CD4 T cell responses to model antigens. Confocal microscopy of infected tissues revealed that many live Salmonella resided alone in infected host macrophages with no damaged Salmonella releasing internal antigens in their vicinity. In the absence of accessible internal antigens, detection of these infected cells might require CD4 T cell recognition of Salmonella surface-associated antigens that could be processed and presented even from intact Salmonella. In conclusion, our findings might pave the way for development of an efficacious Salmonella vaccine with broad serovar coverage, and suggest a similar crucial role of surface antigens for immunity to both extracellular and intracellular pathogens.

【 授权许可】

CC BY