Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummary
Background & Aims: Systemic cellular immunity elicited by the Ty21a oral typhoid vaccine has been extensively characterized. However, very limited data are available in humans regarding mucosal immunity at the site of infection (terminal ileum [TI]). Here we investigated the host immunity elicit...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-11-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X17301327 |
| _version_ | 1818561185376632832 |
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| author | Jayaum S. Booth Seema A. Patil Leyla Ghazi Robin Barnes Claire M. Fraser Alessio Fasano Bruce D. Greenwald Marcelo B. Sztein |
| author_facet | Jayaum S. Booth Seema A. Patil Leyla Ghazi Robin Barnes Claire M. Fraser Alessio Fasano Bruce D. Greenwald Marcelo B. Sztein |
| author_sort | Jayaum S. Booth |
| collection | DOAJ |
| description | Background & Aims: Systemic cellular immunity elicited by the Ty21a oral typhoid vaccine has been extensively characterized. However, very limited data are available in humans regarding mucosal immunity at the site of infection (terminal ileum [TI]). Here we investigated the host immunity elicited by Ty21a immunization on terminal ileumâlamina propria mononuclear cells (LPMC) and peripheral blood in volunteers undergoing routine colonoscopy. Methods: We characterized LPMC-T memory (TM) subsets and assessed Salmonella enterica serovar Typhi (S Typhi)âspecific responses by multichromatic flow cytometry. Results: No differences were observed in cell yields and phenotypes in LPMC CD8+-TM subsets following Ty21a immunization. However, Ty21a immunization elicited LPMC CD8+ T cells exhibiting significant S Typhiâspecific responses (interferon-γ, tumor necrosis factor-α, interleukin-17A, and/or CD107a) in all major TM subsets (T-effector/memory [TEM], T-central/memory, and TEM-CD45RA+), although each TM subset exhibited unique characteristics. We also investigated whether Ty21a immunization elicited S Typhiâspecific multifunctional effectors in LPMC CD8+ TEM. We observed that LPMC CD8+ TEM responses were mostly multifunctional, except for those cells exhibiting the characteristics associated with cytotoxic responses. Finally, we compared mucosal with systemic responses and made the important observation that LPMC CD8+ S Typhiâspecific responses were unique and distinct from their systemic counterparts. Conclusions: This study provides the first demonstration of S Typhiâspecific responses in the human terminal ileum mucosa and provides novel insights into the generation of mucosal immune responses following oral Ty21a immunization. Keywords: Lamina Propria Mononuclear Cells, Multifunctional T Cells, CD8+-T Memory Cells, Typhoid, Vaccines |
| first_indexed | 2024-12-14T00:47:37Z |
| format | Article |
| id | doaj.art-16fc4f1d0f9247cebf266bd755964326 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-14T00:47:37Z |
| publishDate | 2017-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-16fc4f1d0f9247cebf266bd7559643262022-12-21T23:24:01ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2017-11-0143419437Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummaryJayaum S. Booth0Seema A. Patil1Leyla Ghazi2Robin Barnes3Claire M. Fraser4Alessio Fasano5Bruce D. Greenwald6Marcelo B. Sztein7Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MarylandDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MarylandDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MarylandCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, MarylandDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MarylandMucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MassachusettsDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MarylandCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland; Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Correspondence Address correspondence to: Dr. Marcelo B. Sztein, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201. fax: (410) 706 6205.Background & Aims: Systemic cellular immunity elicited by the Ty21a oral typhoid vaccine has been extensively characterized. However, very limited data are available in humans regarding mucosal immunity at the site of infection (terminal ileum [TI]). Here we investigated the host immunity elicited by Ty21a immunization on terminal ileumâlamina propria mononuclear cells (LPMC) and peripheral blood in volunteers undergoing routine colonoscopy. Methods: We characterized LPMC-T memory (TM) subsets and assessed Salmonella enterica serovar Typhi (S Typhi)âspecific responses by multichromatic flow cytometry. Results: No differences were observed in cell yields and phenotypes in LPMC CD8+-TM subsets following Ty21a immunization. However, Ty21a immunization elicited LPMC CD8+ T cells exhibiting significant S Typhiâspecific responses (interferon-γ, tumor necrosis factor-α, interleukin-17A, and/or CD107a) in all major TM subsets (T-effector/memory [TEM], T-central/memory, and TEM-CD45RA+), although each TM subset exhibited unique characteristics. We also investigated whether Ty21a immunization elicited S Typhiâspecific multifunctional effectors in LPMC CD8+ TEM. We observed that LPMC CD8+ TEM responses were mostly multifunctional, except for those cells exhibiting the characteristics associated with cytotoxic responses. Finally, we compared mucosal with systemic responses and made the important observation that LPMC CD8+ S Typhiâspecific responses were unique and distinct from their systemic counterparts. Conclusions: This study provides the first demonstration of S Typhiâspecific responses in the human terminal ileum mucosa and provides novel insights into the generation of mucosal immune responses following oral Ty21a immunization. Keywords: Lamina Propria Mononuclear Cells, Multifunctional T Cells, CD8+-T Memory Cells, Typhoid, Vaccineshttp://www.sciencedirect.com/science/article/pii/S2352345X17301327 |
| spellingShingle | Jayaum S. Booth Seema A. Patil Leyla Ghazi Robin Barnes Claire M. Fraser Alessio Fasano Bruce D. Greenwald Marcelo B. Sztein Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummary Cellular and Molecular Gastroenterology and Hepatology |
| title | Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummary |
| title_full | Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummary |
| title_fullStr | Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummary |
| title_full_unstemmed | Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummary |
| title_short | Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in HumansSummary |
| title_sort | systemic and terminal ileum mucosal immunity elicited by oral immunization with the ty21a typhoid vaccine in humanssummary |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X17301327 |
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