Use of a novel antigen expressing system to study the Salmonella enterica serovar Typhi protein recognition by T cells

Salerno-Gonçalves, Rosângela; Tettelin, Hervé; Lou, David; Steiner, Stephanie; Rezwanul, Tasmia; Guo, Quanquan; Picking, William D.; Nene, Vishvanath; Sztein, Marcelo B.

doi:10.1371/journal.pntd.0005912

Cited by 9 publications

(27 citation statements)

References 57 publications

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“…The type of antigen used for in vitro stimulation influence the responses of CD4+T M . Thus, we addressed this issue by using S. Typhi-infected targets (moderately efficient CD4+ T stimulation) and Ty21a homogenate antigens (an efficient CD4+ T stimulation) [51] to stimulate CD4+T RM subsets. Remarkably, our results indicate that following stimulation with Ty21a homogenate antigens, LPMC CD103+T RM largely produced significantly higher levels of S. Typhi-specific IFNγ-MF, IL-2-MF and TNFα-MF in Ty21a vaccinated participants than those in the unvaccinated group.…”

Section: Discussionmentioning

confidence: 99%

Oral typhoid vaccine Ty21a elicits antigen-specific resident memory CD4+ T cells in the human terminal ileum lamina propria and epithelial compartments

et al. 2020

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Background: Salmonella enterica serovar Typhi (S. Typhi) is a highly invasive bacterium that infects the human intestinal mucosa and causes ~ 11.9-20.6 million infections and ~ 130,000-223,000 deaths annually worldwide. Oral typhoid vaccine Ty21a confers a moderate level of long-lived protection (5-7 years) in the field. New and improved vaccines against enteric pathogens are needed but their development is hindered by a lack of the immunological correlates of protection especially at the site of infection. Tissue resident memory T (T RM ) cells provide immediate adaptive effector immune responsiveness at the infection site. However, the mechanism(s) by which S. Typhi induces T RM in the intestinal mucosa are unknown. Here, we focus on the induction of S. Typhi-specific CD4+T RM subsets by Ty21a in the human terminal ileum lamina propria and epithelial compartments. Methods:Terminal ileum biopsies were obtained from consenting volunteers undergoing routine colonoscopy who were either immunized orally with 4 doses of Ty21a or not. Isolated lamina propria mononuclear cells (LPMC) and intraepithelial lymphocytes (IEL) CD4+T RM immune responses were determined using either S. Typhi-infected or noninfected autologous EBV-B cell lines as stimulator cells. T-CMI was assessed by the production of 4 cytokines [interferon (IFN)γ, interleukin (IL)-2, IL-17A and tumor necrosis factor (TNF)α] in 36 volunteers (18 vaccinees and 18 controls volunteers). Results:Although the frequencies of LPMC CD103+ CD4+T RM were significant decreased, both CD103+ and CD103− CD4+T RM subsets spontaneously produced significantly higher levels of cytokines (IFNγ and IL-17A) following Ty21a-immunization. Importantly, we observed significant increases in S. Typhi-specific LPMC CD103+ CD4+T RM (IFNγ and IL-17A) and CD103− CD4+T RM (IL-2 and IL-17A) responses following Ty21a-immunization. Further, differences in S. Typhi-specific responses between these two CD4+T RM subsets were observed following multifunctional analysis. In addition, we determined the effect of Ty21a-immunization on IEL and observed significant changes in the frequencies of IEL CD103+ (decrease) and CD103− CD4+T RM (increase) following immunization. Finally, we observed that IEL CD103− CD4+T RM , but not CD103+ CD4+T RM , produced increased cytokines (IFNγ, TNFα and IL-17A) to S. Typhi-specific stimulation following Ty21a-immunization. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article' Conclusions: Oral Ty21a-immunization elicits distinct compartment sp...

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Section: Discussionmentioning

confidence: 99%

Oral typhoid vaccine Ty21a elicits antigen-specific resident memory CD4+ T cells in the human terminal ileum lamina propria and epithelial compartments

et al. 2020

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“…Autologous target cells (EBV-B) generated as described above were infected with wt S. Typhi strain (ISP1820, Vi + , a clinical isolate from Chile) (16) at a multiplicity of infection of 7:1 as previously described (9, 22, 30). Briefly, the targets and bacteria were incubated for 3 h at 37°C in RPMI without antibiotics, washed three times with cRMPI and incubated overnight with cRPMI containing 150 μg ml −1 gentamicin.…”

Section: Methodsmentioning

confidence: 99%

“…The recombinant and purified S . Typhi FliC was prepared as described previously (16). Briefly, the FliC encoding region (residues 53–450) was subcloned from S .…”

Section: Methodsmentioning

confidence: 99%

Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4+ T memory responses in humans

Booth

Goldberg

Patil

et al. 2018

International Immunology

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“…For example, they are major components of OM vesicles released by bacteria and can play a role during inflammation and response of the host immune system [7][8][9][10][11] .…”

Section: Ompf and Ompc Orthologs Are Present In Closely Related Entermentioning

confidence: 99%

Porins and small-molecule translocation across the outer membrane of Gram-negative bacteria

Vergalli¹,

Bodrenko²,

Masi³

et al. 2019

Nat Rev Microbiol

262

260

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Gram-negative bacteria and their complex cell envelope comprising an outer and inner membrane are an important and attractive system for studying the translocation of small molecules across biological membranes. In the outer membrane of Enterobacteriaceae, trimeric porins control the cellular penetration of small molecules, including nutrients and antibacterial agents. The synergistic action between relatively slow porin-mediated passive uptake across the outer membrane and active efflux transporters in the inner membrane creates a permeability barrier that reinforces the enzymatic modification barrier, which efficiently reduces the intracellular concentrations of small molecules and contributes to the emergence of antibiotic resistance. In this review, we discuss recent advances in our understanding of the molecular and functional roles of classic porins in small molecule translocation in Enterobacteriaceae and consider the crucial role of porins in antibiotic resistance. Commented [w1]: Is this specification necessary here?, in my opinion it deviates, better to put later… Commented [JP2]: Editor request... porins represent the preferred route for the entry of β-lactams, including cephalosporins, penicillins and carbapenems 14-16. The clinical relevance of membrane-associated mechanisms (MAMs) of resistance (i.e. porin defects and/or overexpression of multidrug efflux pumps) has been well established for these antibiotics. The Influx and Efflux rates control the internal concentration of antibiotics and represent the first lane (mechanical barrier) protecting the bacterial cells against therapeutic treatment 1-3,6. Consequently, studies on bacterial porins are receiving a renewed interest due to their key role in the bacterial susceptibility towards clinically used antibiotics. In combination with the expression of antibiotic-modifying enzymes expressed in the periplasm (e.g. β-lactamases), porins play a key role in β-lactam resistance 4,17. In this review, we discuss recent advances in our understanding of the molecular and functional roles of classic porins in antibiotic translocation in Enterobacteriaceae. We explore structural aspects and the insights gained into permeation and the pore translocation process, the regulation of porin expression as well as the role of porins in the emergence of antibiotic susceptibility. Enterobacterial general porins Structural aspects The crystal structures of a general porin from Rhodobacter capsulatus 18 , the OmpF and PhoE porins from E. coli 19 and other E. coli OmpF structures including mutants 20,21 were the first to be solved. Only a limited number of other enterobacterial porin structures have been reported, i.e. E. coli OmpC, K. pneumoniae OmpK36 and Salmonella typhi OmpF 22-24. The lack of data has hindered attempts to relate structure to function. Recently, the structures of two porins from P. stuartii as well as the structures of the OmpF and OmpC orthologs of K. pneumoniae, E. aerogenes and E. cloacae have been reported 12,25,26. Another recent study reported th...

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Use of a novel antigen expressing system to study the Salmonella enterica serovar Typhi protein recognition by T cells

Cited by 9 publications

References 57 publications

Oral typhoid vaccine Ty21a elicits antigen-specific resident memory CD4+ T cells in the human terminal ileum lamina propria and epithelial compartments

Oral typhoid vaccine Ty21a elicits antigen-specific resident memory CD4+ T cells in the human terminal ileum lamina propria and epithelial compartments

Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4+ T memory responses in humans

Porins and small-molecule translocation across the outer membrane of Gram-negative bacteria

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