Oral Challenge with Wild-type Salmonella Typhi Induces Distinct Changes in B cell Subsets in Individuals Who Develop Typhoid Disease

A new human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently developed. In this model, 10⁴ CFU resulted in 65% of participants developing typhoid fever (TD) 5-10 days post-challenge. TD was diagnosed in participants meeting clinical (≥38°C for ≥12h) and/or microbiological (bacteremia) endpoints. Changes in B cells subpopulations following S. Typhi challenge remain to be explored. To address this, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD-) was evaluated. The most notable changes included an increase in plasmablasts frequency during disease days (TD-0h to TD-96h).  Plasmablasts also showed enhanced binding to S. Typhi, decreased expression of IgA and increased expression of CD21. Additionally, the percentages of B memory subsets (IgD/CD27 classification) were decreased during disease days, most notably in switched (Sm) and unswitched (Um) memory cells. Of note, IgA expression was upregulated in Sm cells. Moreover, the percentages of Sm CD27+ cells phosphorylating Erk1/2, p38MAPK and Btk were increased during disease days. These changes were absent in NoTD volunteers. This is the first study to describe differences in B cell subsets related directly to clinical outcome following oral challenge with wild-type S. Typhi.