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Background  Nontyphoidal  Salmonellae  frequently cause life-threatening bacteremia in sub-Saharan Africa. Young children and HIV-infected adults are particularly susceptible. High case-fatality rates and increasing antibiotic resistance require new approaches to the management of this disease. Impaired cellular immunity caused by defects in the T helper 1 pathway lead to intracellular disease with  Salmonella  that can be countered by IFNγ administration. This report identifies the lymphocyte subsets that produce IFNγ early in  Salmonella  infection.    Methodology  Intracellular cytokine staining was used to identify IFNγ production in blood lymphocyte subsets of ten healthy adults with antibodies to  Salmonella  (as evidence of immunity to  Salmonella ), in response to stimulation with live and heat-killed preparations of the D23580 invasive African isolate of  Salmonella  Typhimurium. The absolute number of IFNγ-producing cells in innate, innate-like and adaptive lymphocyte subpopulations was determined.    Principal Findings  Early IFNγ production was found in the innate/innate-like lymphocyte subsets: γδ-T cells, NK cells and NK-like T cells. Significantly higher percentages of such cells produced IFNγ compared to adaptive αβ-T cells (Student's t test,  P <0.001 and ≤0.02 for each innate subset compared, respectively, with CD4 + - and CD8 + -T cells). The absolute numbers of IFNγ-producing cells showed similar differences. The proportion of IFNγ-producing γδ-T cells, but not other lymphocytes, was significantly higher when stimulated with live compared with heat-killed bacteria ( P <0.0001).    Conclusion/Significance  Our findings indicate an inherent capacity of innate/innate-like lymphocyte subsets to produce IFNγ early in the response to  Salmonella  infection. This may serve to control intracellular infection and reduce the threat of extracellular spread of disease with bacteremia which becomes life-threatening in the absence of protective antibody. These innate cells may also help mitigate against the effect on IFNγ production of depletion of  Salmonella -specific CD4 + -T lymphocytes in HIV infection.

Early Interferon-γ Production in Human Lymphocyte Subsets in Response to Nontyphoidal Salmonella Demonstrates Inherent Capacity in Innate Cells