Sequential Acquisition of T Cells and Antibodies to Nontyphoidal Salmonella in Malawian Children



Nyirenda, Tonney S, Gilchrist, James J, Feasey, Nicholas A, Glennie, Sarah J, Bar-Zeev, Naor ORCID: 0000-0003-0570-4624, Gordon, Melita ORCID: 0000-0002-0629-0884, MacLennan, Calman A, Mandala, Wilson L and Heyderman, Robert S
(2014) Sequential Acquisition of T Cells and Antibodies to Nontyphoidal Salmonella in Malawian Children. The Journal of Infectious Diseases, 210 (1). 56 - 64.

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Abstract

Background. Salmonella Typhimurium (STm) remain a prominent cause of bacteremia in sub-Saharan Africa. Complement-fixing antibodies to STm develop by 2 years of age. We hypothesized that STm-specific CD4+ T cells develop alongside this process. Methods. Eighty healthy Malawian children aged 0–60 months were recruited. STm-specific CD4+ T cells producing interferon γ, tumor necrosis factor α, and interleukin 2 were quantified using intracellular cytokine staining. Antibodies to STm were measured by serum bactericidal activity (SBA) assay, and anti-STm immunoglobulin G antibodies by enzyme-linked immunosorbent assay. Results. Between 2006 and 2011, STm bacteremias were detected in 449 children <5 years old. STm-specific CD4+ T cells were acquired in infancy, peaked at 14 months, and then declined. STm-specific SBA was detectable in newborns, declined in the first 8 months, and then increased to a peak at age 35 months. Acquisition of SBA correlated with acquisition of anti–STm–lipopolysaccharide (LPS) immunoglobulin G (r = 0.329 [95% confidence interval, .552–.062]; P = .01) but not anti–STm–outer membrane protein or anti–STm-flagellar protein (FliC). Conclusions. Acquisition of STm-specific CD4+ T cells in early childhood is consistent with early exposure to STm or cross-reactive protein antigens priming this T-cell development. STm-specific CD4+ T cells seem insufficient to protect against invasive nontyphoidal Salmonella disease, but sequential acquisition of SBA to STm LPS is associated with a decline in its incidence.

Item Type: Article
Uncontrolled Keywords: Salmonella, T cell, antibody, cytokine, children
Subjects: ?? R1 ??
Depositing User: Symplectic Admin
Date Deposited: 15 Sep 2015 08:12
Last Modified: 11 Oct 2021 19:10
DOI: 10.1093/infdis/jiu045
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/2025667