title: Interferon-γ and proliferation responses to Salmonella enterica Serotype Typhi proteins in patients with S. Typhi Bacteremia in Dhaka, Bangladesh.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh.
authors.forename: Alaullah
authors.initials: A
authors.lastname: Sheikh
authors.forename: Farhana
authors.initials: F
authors.lastname: Khanam
authors.forename: Md Abu
authors.initials: MA
authors.lastname: Sayeed
authors.forename: Taibur
authors.initials: T
authors.lastname: Rahman
authors.forename: Marcin
authors.initials: M
authors.lastname: Pacek
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Hu
authors.forename: Andrea
authors.initials: A
authors.lastname: Rollins
authors.forename: Md Saruar
authors.initials: MS
authors.lastname: Bhuiyan
authors.forename: Sean
authors.initials: S
authors.lastname: Rollins
authors.forename: Anuj
authors.initials: A
authors.lastname: Kalsy
authors.forename: Mohammad
authors.initials: M
authors.lastname: Arifuzzaman
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Leung
authors.forename: David A
authors.initials: DA
authors.lastname: Sarracino
authors.forename: Bryan
authors.initials: B
authors.lastname: Krastins
authors.forename: Richelle C
authors.initials: RC
authors.lastname: Charles
authors.forename: Regina C
authors.initials: RC
authors.lastname: Larocque
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cravioto
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Calderwood
authors.forename: W Abdullah
authors.initials: WA
authors.lastname: Brooks
authors.forename: Jason B
authors.initials: JB
authors.lastname: Harris
authors.forename: Joshua
authors.initials: J
authors.lastname: Labaer
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
authors.forename: Edward T
authors.initials: ET
authors.lastname: Ryan
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D016470:Bacteremia / Q000276:immunology* / Q000382:microbiology; D001459:Bangladesh; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008875:Middle Aged; D012485:Salmonella typhi / Q000276:immunology*; D014435:Typhoid Fever / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D007371:Interferon-gamma