Sequential acquisition of T cells and antibodies to nontyphoidal Salmonella in Malawian children.
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.
Tonney S
TS
Nyirenda
James J
JJ
Gilchrist
Nicholas A
NA
Feasey
Sarah J
SJ
Glennie
Naor
N
Bar-Zeev
Melita A
MA
Gordon
Calman A
CA
MacLennan
Wilson L
WL
Mandala
Robert S
RS
Heyderman
D000906:Antibodies / Q000097:blood*; D001770:Blood Bactericidal Activity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008295:Malawi / Q000453:epidemiology; D008297:Male; D012480:Salmonella Infections / Q000453:epidemiology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000906:Antibodies; D007074:Immunoglobulin G; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma