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.
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.
Samandari
T
T
Center for Vaccine Development, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Kotloff
K L
KL
Losonsky
G A
GA
Picking
W D
WD
Sansonetti
P J
PJ
Levine
M M
MM
Sztein
M B
MB
D018829:Adhesins, Bacterial; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000921:Antibody-Producing Cells / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015169:Colony Count, Microbial; D004306:Dose-Response Relationship, Immunologic; D004405:Dysentery, Bacillary / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D017353:Gene Deletion; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis; D019409:Interleukin-15 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008213:Lymphocyte Activation; D022603:Shiga Toxins; D012762:Shigella dysenteriae / Q000235:genetics / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D019409:Interleukin-15; D007376:Interleukin-2; D015848:Interleukin-5; D022603:Shiga Toxins; D016212:Transforming Growth Factor beta; D014614:Vaccines, Synthetic; C053476:invasin, Yersinia; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma