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

• Published in: The Journal of immunology (1950) Vol. 164; no. 4; pp. 2221 - 2232
• Main Authors: Samandari, T, Kotloff, K L, Losonsky, G A, Picking, W D, Sansonetti, P J, Levine, M M, Sztein, M B
• Format: Journal Article
• Language: English
• Published: United States 15.02.2000
• Subjects: Adhesins, Bacterial; Administration, Oral; Adolescent; Adult; Antibodies, Bacterial - biosynthesis; Antibody-Producing Cells - immunology; Antibody-Producing Cells - metabolism; Bacterial Proteins - administration & dosage; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacterial Toxins - administration & dosage; Bacterial Toxins - genetics; Bacterial Toxins - immunology; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - genetics; Bacterial Vaccines - immunology; Colony Count, Microbial; Dose-Response Relationship, Immunologic; Dysentery, Bacillary - immunology; Dysentery, Bacillary - metabolism; Dysentery, Bacillary - prevention & control; g-Interferon; Gene Deletion; Humans; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Interleukin-12 - biosynthesis; Interleukin-15 - biosynthesis; Interleukin-2 - biosynthesis; Interleukin-4 - biosynthesis; Interleukin-5 - biosynthesis; invasin; invasins; Kinetics; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - microbiology; Lymphocyte Activation; Shiga Toxins; Shigella dysenteriae; Shigella dysenteriae - genetics; Shigella dysenteriae - immunology; Transforming Growth Factor beta - biosynthesis; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.164.4.2221

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.