Broad systemic T cell immunity to Salmonella enterica serovar Typhi in U.S. healthy adults
- 1Center for Vaccine Development and Global Health, University of Maryland School of Medicine , , ,
Abstract
Introduction: T cell mediated immunity (T-CMI) is an important component of effective host immunity against intracellular pathogens such as Salmonella enterica serovar Typhi ( S. Typhi; ST). Baseline T-CMI responsiveness to S. Typhi has been previously described in healthy individuals, likely reflecting cross-reactive responsiveness to other Enterobacteriaceae within the gut microbiota. Interestingly, T cell baseline responsiveness has been associated with protection or susceptibility in a human challenge model following exposure to wild-type (wt) ST. To better understand the contribution of this baseline responsiveness to immunity against ST infection, an in-depth characterization of T cell immunity is needed.
Methods: Here, peripheral blood mononuclear cells from eighteen healthy volunteers with no history of typhoid fever vaccination or infection were co-cultured with autologous B-lymphoblastoid cell lines (B-LCL) previously infected with wt ST as antigen presenting cells. Non-infected B-LCL (NI) were used as controls. After 18 h or 40 h of stimulation, cells were stained with a 52-parameter mass cytometry antibody panel and analyzed using manual gating, dimensionality reduction and unsupervised clustering approaches. We studied conventional CD4 ⁺ and CD8 ⁺ T memory cells, including T effector memory (T EM ), T EM re-expressing CD45RA (T EMRA ), and T central memory (T CM ), CD4 ⁺ and CD8 ⁺ T stem cell memory (T SCM ), CD4 ⁺ circulating T follicular helper (cT FH ), CD4 ⁺ T regulatory (T reg ), and CD8 ⁺ T regulatory precursors (T rp ), as well as non-conventional CD8 ⁺ mucosal associated invariant T (MAIT), T gamma delta (Tγδ), and Natural-Killer T (NKT) cells.
Results: All studied cell subsets showed significant (p<0.01) baseline responsiveness to ST-infected target cells when compared to NI target cells. Most functional responses were observed in activation, homing, and cytotoxicity markers across all conventional and non-conventional T cell subsets, defining in great depth the characteristics of baseline T-CMI to S. Typhi.
Discussion: This high-dimensional approach showed a complex interaction between distinct cell subsets with multifunctional properties and extended previous insights into the baseline T-CMI to S. Typhi. This will help guide future investigations of immunity in healthy individuals following infection or vaccination.
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BibTeX
@article{carretobinaghi2026broad,
title = {{Broad systemic T cell immunity to Salmonella enterica serovar Typhi in U.S. healthy adults}},
author = {Laura E. Carreto-Binaghi and Jayaum S. Booth and Rezwanul Wahid and Rosangela Salerno-Goncalves and Franklin R. Toapanta and Marcelo B. Sztein},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1940148},
url = {https://europepmc.org/article/PMC/PMC13669112},
note = {CC BY},
}
RIS
TY - JOUR
TI - Broad systemic T cell immunity to Salmonella enterica serovar Typhi in U.S. healthy adults
AU - Laura E. Carreto-Binaghi
AU - Jayaum S. Booth
AU - Rezwanul Wahid
AU - Rosangela Salerno-Goncalves
AU - Franklin R. Toapanta
AU - Marcelo B. Sztein
PY - 2026
DA - 2026/10/01
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1940148
UR - https://europepmc.org/article/PMC/PMC13669112
AB - Introduction: T cell mediated immunity (T-CMI) is an important component of effective host immunity against intracellular pathogens such as Salmonella enterica serovar Typhi ( S. Typhi; ST). Baseline T-CMI responsiveness to S. Typhi has been previously described in healthy individuals, likely reflecting cross-reactive responsiveness to other Enterobacteriaceae within the gut microbiota. Interestingly, T cell baseline responsiveness has been associated with protection or susceptibility in a human challenge model following exposure to wild-type (wt) ST. To better understand the contribution of this baseline responsiveness to immunity against ST infection, an in-depth characterization of T cell immunity is needed. Methods: Here, peripheral blood mononuclear cells from eighteen healthy volunteers with no history of typhoid fever vaccination or infection were co-cultured with autologous B-lymphoblastoid cell lines (B-LCL) previously infected with wt ST as antigen presenting cells. Non-infected B-LCL (NI) were used as controls. After 18 h or 40 h of stimulation, cells were stained with a 52-parameter mass cytometry antibody panel and analyzed using manual gating, dimensionality reduction and unsupervised clustering approaches. We studied conventional CD4 ⁺ and CD8 ⁺ T memory cells, including T effector memory (T EM ), T EM re-expressing CD45RA (T EMRA ), and T central memory (T CM ), CD4 ⁺ and CD8 ⁺ T stem cell memory (T SCM ), CD4 ⁺ circulating T follicular helper (cT FH ), CD4 ⁺ T regulatory (T reg ), and CD8 ⁺ T regulatory precursors (T rp ), as well as non-conventional CD8 ⁺ mucosal associated invariant T (MAIT), T gamma delta (Tγδ), and Natural-Killer T (NKT) cells. Results: All studied cell subsets showed significant (p<0.01) baseline responsiveness to ST-infected target cells when compared to NI target cells. Most functional responses were observed in activation, homing, and cytotoxicity markers across all conventional and non-conventional T cell subsets, defining in great depth the characteristics of baseline T-CMI to S. Typhi. Discussion: This high-dimensional approach showed a complex interaction between distinct cell subsets with multifunctional properties and extended previous insights into the baseline T-CMI to S. Typhi. This will help guide future investigations of immunity in healthy individuals following infection or vaccination.
SN - 1664-3224
ER -