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

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Nyirenda, T. S., Gilchrist, J. J., Feasey, Nicholas ORCID: https://orcid.org/0000-0003-4041-1405, Glennie, S. J., Bar-Zeev, N., Gordon, M. A., MacLennan, C. A., Mandala, W. L. and Heyderman, R. S. (2014) 'Sequential Acquisition of T Cells and Antibodies to Nontyphoidal Salmonella in Malawian Children'. Journal of Infectious Disease, Vol 210, Issue 1, pp. 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
Subjects: QU Biochemistry > Cells and Genetics > QU 350 Cellular structures
QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies
WC Communicable Diseases > Infection. Bacterial Infections > Enteric Infections > WC 269 Salmonella infections
WS Pediatrics > WS 20 Research (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1093/infdis/jiu045
Depositing User: Lynn Roberts-Maloney
Date Deposited: 02 Apr 2015 11:10
Last Modified: 07 Dec 2018 10:05
URI: https://archive.lstmed.ac.uk/id/eprint/5058

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