Cellular and Cytokine Responses to Salmonella enterica Serotype Typhi Proteins in Patients with Typhoid Fever in Bangladesh

Saruar Bhuiyan,Joshua Labaer,Abu Sayeed,Richelle C Charles,Stephen B Calderwood,Farhana Khanam,Regina C Larocque,Jason B Harris,Umme Salma,Daniel T Leung,Marcin Pacek,Taufiqur Rahman Bhuiyan,Firdausi Qadri,Edward T Ryan,Alaullah Sheikh

doi:10.4269/ajtmh.13-0261

Saruar Bhuiyan, Joshua Labaer + Show 13 more

Open Access

https://doi.org/10.4269/ajtmh.13-0261

Copy DOI

Abstract

We assessed interferon-gamma (IFN-γ) responses via enzyme-linked immunosorbent spot (ELISPOT) to a number of S. Typhi antigens in samples from humans with S. Typhi bacteremia and typhoid fever in Bangladesh. Compared with responses in healthy endemic zone controls, there were significantly increased IFN-γ responses at the time of clinical presentation (acute phase) and at convalescence 14–28 days later. The majority (80–90%) of IFN-γ expressing T cells were CD4+. We observed a significant increase in interleukin-17 (IL-17) positive CD4 + T cells at convalescent versus acute stage of infection using an intracellular cytokine staining assay. We also found that stimulated peripheral blood mononuclear cells (PBMCs) produced significantly increased levels of a number of cytokines at the convalescent versus acute phase of infection, including IFN-γ, MIP-1β, sCD40L, TNF-β, IL-13, and IL-9. These results suggest that S. Typhi antigens induce a predominantly Th1 response, but that elevations in other cytokines may be modulatory.

Highlights

Typhoid fever is a systemic illness caused by infection with Salmonella enterica serotype Typhi, a Gram-negative intracellular bacterium
Typhimurium, it has been shown that interferongamma (IFN-g) produced by Th1 cells plays an important role in bacterial killing, and depletion of Th1-associated cytokines (i.e., IFN-g, interleukin-12 [IL-12], or tumor necrosis factor a [TNF-a]) reduces the protective immune response conferred by attenuated live Salmonella vaccines.[4]
Using the enzyme-linked immunosorbent spot (ELISPOT) method, we found significantly increased IFN-g responses at both acute and convalescent stages of infection upon stimulation with all S

Summary

Introduction

Typhoid fever is a systemic illness caused by infection with Salmonella enterica serotype Typhi, a Gram-negative intracellular bacterium. Typhi infection performed in the 1960s and 1970s suggested a key role for cellular immune responses; these studies were performed before the availability of modern immunologic techniques.[2] Our current understanding of cellular responses during S. Typhi live vaccine strains.[3] From murine studies with S. Typhimurium, it has been shown that interferongamma (IFN-g) produced by Th1 cells plays an important role in bacterial killing, and depletion of Th1-associated cytokines (i.e., IFN-g, interleukin-12 [IL-12], or tumor necrosis factor a [TNF-a]) reduces the protective immune response conferred by attenuated live Salmonella vaccines.[4] In healthy North American volunteers, oral ingestion of live attenuated S. Typhi antigens.[5,6]

Methods

Results

Conclusion