Interferon-γ and proliferation responses to Salmonella enterica Serotype Typhi proteins in patients with S. Typhi Bacteremia in Dhaka, Bangladesh

Autor: Firdausi Qadri, Regina C. LaRocque, Alejandro Cravioto, Joshua LaBaer, Stephen B. Calderwood, Yanhui Hu, Edward T. Ryan, Md. Abu Sayeed, Jason B. Harris, Andrea Rollins, Marcin Pacek, Mohammad Arifuzzaman, Md. Saruar Bhuiyan, Sean M. Rollins, Bryan Krastins, Alaullah Sheikh, Daniel T. Leung, Taibur Rahman, David A. Sarracino, Anuj Kalsy, Farhana Khanam, Richelle C. Charles, W. Abdullah Brooks
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Serotype
Salmonella
Salmonella infection
Bacteremia
medicine.disease_cause
Salmonella typhi
0302 clinical medicine
Child
Immune Response
Cells
Cultured
0303 health sciences
Bangladesh
T Cells
lcsh:Public aspects of medicine
Middle Aged
3. Good health
Bacterial Pathogens
Infectious Diseases
Salmonella enterica
Child
Preschool
Antibody
Research Article
Adult
lcsh:Arctic medicine. Tropical medicine
Adolescent
lcsh:RC955-962
Immune Cells
Immunology
Biology
Microbiology
Typhoid fever
03 medical and health sciences
Interferon-gamma
Young Adult
Antigen
medicine
Humans
Typhoid Fever
030304 developmental biology
Cell Proliferation
Antigens
Bacterial
Public Health
Environmental and Occupational Health
Infant
lcsh:RA1-1270
medicine.disease
biology.organism_classification
Virology
biology.protein
Leukocytes
Mononuclear
bacteria
030215 immunology
Zdroj: PLoS Neglected Tropical Diseases, Vol 5, Iss 6, p e1193 (2011)
PLoS Neglected Tropical Diseases
ISSN: 1935-2735
1935-2727
Popis: Background Salmonella enterica serotype Typhi is a human-restricted intracellular pathogen and the cause of typhoid fever. Cellular immune responses are required to control and clear Salmonella infection. Despite this, there are limited data on cellular immune responses in humans infected with wild type S. Typhi. Methodology/Principal Findings For this work, we used an automated approach to purify a subset of S. Typhi proteins identified in previous antibody-based immuno-affinity screens and antigens known to be expressed in vivo, including StaF-putative fimbrial protein-STY0202, StbB-fimbrial chaperone-STY0372, CsgF-involved in curli production-STY1177, CsgD- putative regulatory protein-STY1179, OppA-periplasmic oligopeptide binding protein precursor-STY1304, PagC-outer membrane invasion protein-STY1878, and conserved hypothetical protein-STY2195; we also generated and analyzed a crude membrane preparation of S. Typhi (MP). In comparison to samples collected from uninfected Bangladeshi and North American participants, we detected significant interferon-γ responses in PBMCs stimulated with MP, StaF, StbB, CsgF, CsgD, OppA, STY2195, and PagC in patients bacteremic with S. Typhi in Bangladesh. The majority of interferon-γ expressing T cells were CD4 cells, although CD8 responses also occurred. We also assessed cellular proliferation responses in bacteremic patients, and confirmed increased responses in infected individuals to MP, StaF, STY2195, and PagC in convalescent compared to acute phase samples and compared to controls. StaF is a fimbrial protein homologous to E. coli YadK, and contains a Pfam motif thought to be involved in cellular adhesion. PagC is expressed in vivo under the control of the virulence-associated PhoP-regulon required for intra-macrophage survival of Salmonella. STY2195 is a conserved hypothetical protein of unknown function. Conclusion/Significance This is the first analysis of cellular immune responses to purified S. Typhi antigens in patients with typhoid fever. These results indicate that patients generate significant CD4 and CD8 interferon-γ responses to specific S. Typhi antigens during typhoid fever, and that these responses are elevated at the time of clinical presentation. These observations suggest that an interferon-γ based detection system could be used to diagnose individuals with typhoid fever during the acute stage of illness.
Author Summary Salmonella enterica serotype Typhi infection is a significant global public health problem and the cause of typhoid fever. Salmonella are intracellular pathogens, and cellular immune responses are required to control and clear Salmonella infections. Despite this, there are limited data on cellular immune responses during wild type S. Typhi infection in humans. Here we report the assessment of cellular immune responses in humans with S. Typhi bacteremia through a screening approach that permitted us to evaluate interferon-γ and proliferation responses to a number of S. Typhi antigens. We detected significant interferon-γ CD4 and CD8 responses, as well as proliferative responses, to a number of recombinantly purified S. Typhi proteins as well as membrane preparation in infected patients. Antigen-specific interferon-γ responses were present at the time of clinical presentation in patients and absent in healthy controls. These observations could assist in the development of interferon-γ-based diagnostic assays for typhoid fever.
Databáze: OpenAIRE
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