1. Production of IFN-gamma and IL-10 to Shigella invasins by mononuclear cells from volunteers orally inoculated with a Shiga toxin-deleted Shigella dysenteriae type 1 strain.
- Author
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Samandari T, Kotloff KL, Losonsky GA, Picking WD, Sansonetti PJ, Levine MM, and Sztein MB
- Subjects
- Administration, Oral, Adolescent, Adult, Antibodies, Bacterial biosynthesis, Antibody-Producing Cells immunology, Antibody-Producing Cells metabolism, Bacterial Proteins administration & dosage, Bacterial Proteins genetics, Bacterial Toxins administration & dosage, Bacterial Toxins genetics, Bacterial Vaccines administration & dosage, Bacterial Vaccines genetics, Colony Count, Microbial, Dose-Response Relationship, Immunologic, Dysentery, Bacillary immunology, Dysentery, Bacillary metabolism, Dysentery, Bacillary prevention & control, Gene Deletion, Humans, Interleukin-12 biosynthesis, Interleukin-15 biosynthesis, Interleukin-2 biosynthesis, Interleukin-4 biosynthesis, Interleukin-5 biosynthesis, Kinetics, Leukocytes, Mononuclear metabolism, Leukocytes, Mononuclear microbiology, Lymphocyte Activation, Shiga Toxins, Shigella dysenteriae genetics, Transforming Growth Factor beta biosynthesis, Vaccines, Synthetic administration & dosage, Adhesins, Bacterial, Bacterial Proteins immunology, Bacterial Toxins immunology, Bacterial Vaccines immunology, Interferon-gamma biosynthesis, Interleukin-10 biosynthesis, Leukocytes, Mononuclear immunology, Shigella dysenteriae immunology, Vaccines, Synthetic immunology
- Abstract
Volunteers were orally administered invasive, non-Shiga toxin-producing Shigella dysenteriae 1 to establish a challenge model to assess vaccine efficacy. In stepwise fashion, four separate groups were given 3 x 10(2), 7 x 10(3), 5 x 10(4), or 7 x 10(5) CFU. Using PBMC, proliferative responses and cytokine production were measured to S. dysenteriae whole-cell preparations and to purified recombinant invasion plasmid Ags (Ipa) C and IpaD. Anti-LPS and anti-Ipa Abs and Ab-secreting cells were also evaluated. Preinoculation PBMC produced considerable quantities of IL-10 and IFN-gamma, probably secreted by monocytes and NK cells, respectively, of the innate immune system. Following inoculation, PBMC from 95 and 87% of volunteers exhibited an increased production of IFN-gamma and IL-10, respectively, in response to Shigella Ags. These increases included responses to IpaC and IpaD among those volunteers receiving the lowest inoculum. No IL-4 or IL-5 responses were detected. Whereas there were no Ab or Ab-secreting cell responses in volunteers receiving the lowest inoculum, other dose groups had moderate to strong anti-LPS and anti-Ipa responses. These results suggest that in humans, type 1 responses play an important role in mucosal and systemic immunity to S. dysentariae 1.
- Published
- 2000
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