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

Alaullah Sheikh, Farhana Khanam, Md Abu Sayeed, Taibur Rahman, Marcin Pacek, Yanhui Hu, Andrea Rollins, Md Saruar Bhuiyan, Sean Rollins, Anuj Kalsy, Mohammad Arifuzzaman, Daniel T. Leung, David A. Sarracino, Bryan Krastins, Richelle C. Charles, Regina C. LaRocque, Alejandro Cravioto, Stephen B. Calderwood, W Abdullah Brooks, Jason B. HarrisJoshua LaBaer, Firdausi Qadri, Edward T. Ryan

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Article numbere1193
JournalPLoS Neglected Tropical Diseases
Volume5
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

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Salmonella enterica
Bangladesh
Bacteremia
Interferons
Typhoid Fever
Cellular Immunity
Proteins
Antigens
Periplasmic Binding Proteins
Regulon
Oligopeptides
Protein Precursors
Salmonella Infections
Protein S
Salmonella
Virulence
Membrane Proteins
Macrophages
Cell Proliferation
Serogroup

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Interferon-γ and proliferation responses to Salmonella enterica serotype Typhi proteins in patients with S. Typhi bacteremia in Dhaka, Bangladesh. / Sheikh, Alaullah; Khanam, Farhana; Sayeed, Md Abu; Rahman, Taibur; Pacek, Marcin; Hu, Yanhui; Rollins, Andrea; Bhuiyan, Md Saruar; Rollins, Sean; Kalsy, Anuj; Arifuzzaman, Mohammad; Leung, Daniel T.; Sarracino, David A.; Krastins, Bryan; Charles, Richelle C.; LaRocque, Regina C.; Cravioto, Alejandro; Calderwood, Stephen B.; Brooks, W Abdullah; Harris, Jason B.; LaBaer, Joshua; Qadri, Firdausi; Ryan, Edward T.

In: PLoS Neglected Tropical Diseases, Vol. 5, No. 6, e1193, 06.2011.

Research output: Contribution to journalArticle

Sheikh, A, Khanam, F, Sayeed, MA, Rahman, T, Pacek, M, Hu, Y, Rollins, A, Bhuiyan, MS, Rollins, S, Kalsy, A, Arifuzzaman, M, Leung, DT, Sarracino, DA, Krastins, B, Charles, RC, LaRocque, RC, Cravioto, A, Calderwood, SB, Brooks, WA, Harris, JB, LaBaer, J, Qadri, F & Ryan, ET 2011, 'Interferon-γ and proliferation responses to Salmonella enterica serotype Typhi proteins in patients with S. Typhi bacteremia in Dhaka, Bangladesh', PLoS Neglected Tropical Diseases, vol. 5, no. 6, e1193. https://doi.org/10.1371/journal.pntd.0001193
Sheikh, Alaullah ; Khanam, Farhana ; Sayeed, Md Abu ; Rahman, Taibur ; Pacek, Marcin ; Hu, Yanhui ; Rollins, Andrea ; Bhuiyan, Md Saruar ; Rollins, Sean ; Kalsy, Anuj ; Arifuzzaman, Mohammad ; Leung, Daniel T. ; Sarracino, David A. ; Krastins, Bryan ; Charles, Richelle C. ; LaRocque, Regina C. ; Cravioto, Alejandro ; Calderwood, Stephen B. ; Brooks, W Abdullah ; Harris, Jason B. ; LaBaer, Joshua ; Qadri, Firdausi ; Ryan, Edward T. / Interferon-γ and proliferation responses to Salmonella enterica serotype Typhi proteins in patients with S. Typhi bacteremia in Dhaka, Bangladesh. In: PLoS Neglected Tropical Diseases. 2011 ; Vol. 5, No. 6.
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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. 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 = "Alaullah Sheikh and Farhana Khanam and Sayeed, {Md Abu} and Taibur Rahman and Marcin Pacek and Yanhui Hu and Andrea Rollins and Bhuiyan, {Md Saruar} and Sean Rollins and Anuj Kalsy and Mohammad Arifuzzaman and Leung, {Daniel T.} and Sarracino, {David A.} and Bryan Krastins and Charles, {Richelle C.} and LaRocque, {Regina C.} and Alejandro Cravioto and Calderwood, {Stephen B.} and Brooks, {W Abdullah} and Harris, {Jason B.} and Joshua LaBaer and Firdausi Qadri and Ryan, {Edward T.}",
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TY - JOUR

T1 - Interferon-γ and proliferation responses to Salmonella enterica serotype Typhi proteins in patients with S. Typhi bacteremia in Dhaka, Bangladesh

AU - Sheikh, Alaullah

AU - Khanam, Farhana

AU - Sayeed, Md Abu

AU - Rahman, Taibur

AU - Pacek, Marcin

AU - Hu, Yanhui

AU - Rollins, Andrea

AU - Bhuiyan, Md Saruar

AU - Rollins, Sean

AU - Kalsy, Anuj

AU - Arifuzzaman, Mohammad

AU - Leung, Daniel T.

AU - Sarracino, David A.

AU - Krastins, Bryan

AU - Charles, Richelle C.

AU - LaRocque, Regina C.

AU - Cravioto, Alejandro

AU - Calderwood, Stephen B.

AU - Brooks, W Abdullah

AU - Harris, Jason B.

AU - LaBaer, Joshua

AU - Qadri, Firdausi

AU - Ryan, Edward T.

PY - 2011/6

Y1 - 2011/6

N2 - 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.

AB - 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.

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