Enteral immunization with attenuated recombinant Listeria monocytogenes as a live vaccine vector: organ-dependent dynamics of CD4 T lymphocytes reactive to a Leishmania major tracer epitope.
Listeria monocytogenes is considered as a potential live bacterial vector, particularly for the induction of CD8 T cells. The CD4 T-cell immune response triggered after enteral immunization of mice has not yet been thoroughly characterized. The dynamics of gamma interferon (IFN-gamma)- and interleukin-4 (IL-4)-secreting CD4 T cells were analyzed after priming through intragastric delivery of an attenuated delta actA recombinant L. monocytogenes strain expressing the Leishmania major LACK protein; a peptide of this protein, LACK(158-173) peptide (pLACK), is a well-characterized CD4 T-cell target in BALB/c mice. Five compartments were monitored: Peyer's patches, mesenteric lymph nodes (MLN), spleen, liver, and blood. A single intragastric inoculation of delta actA-LACK-LM in BALB/c mice led to colonization of the MLN and spleen at a significant level for at least 3 days. Efficient priming of IFN-gamma-secreting pLACK-reactive CD4 T cells was observed in all tested compartments. Interestingly, IL-4-secreting pLACK-reactive CD4 T cells were detectable at day 6 or 7 only in blood and liver. The absence of translocation of viable bacteria through the intestinal epithelium after further delta actA-LACK-LM inoculations was concomitant with the absence of an increase in the level of IFN-gamma secreted by the MLN, blood, and splenic pLACK-reactive Th1 T cells, although the levels remained significantly above the basal level. No change in this population size was detected in the spleen. However, an increase in the number of intragastric inoculations had a clinical beneficial effect in L. major-infected BALB/c mice. L. monocytogenes thus presents the potential of an efficient vector for induction of CD4 T cells when administered by the enteral route.
Saklani-Jusforgues
Hélène
H
Unité d'Immunophysiologie et Parasitisme Intracellulaire, Institut Pasteur, Paris, France.
Fontan
Elisabeth
E
Soussi
Neirouz
N
Milon
Geneviève
G
Goossens
Pierre L
PL
D000818:Animals; D000953:Antigens, Protozoan; D018988:Bacterial Translocation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology*; D008089:Listeria monocytogenes / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic; C093139:LACK antigen, Leishmania; D015847:Interleukin-4; D007371:Interferon-gamma