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Skin-draining lymph node priming is sufficient to induce sterile immunity against pre-erythrocytic malaria.

Obeid M, Franetich JF, Lorthiois A, Gego A, Grüner AC, Tefit M, Boucheix C, Snounou G, Mazier D - EMBO Mol Med (2012)

Bottom Line: However, it has recently been demonstrated that priming also occurs in the skin.We wished to establish if sterile protection could be obtained in the absence of priming by infected hepatocytes.We then compared and contrasted the patterns of priming with those obtained by intradermal immunization, where priming occurs in the liver.

View Article: PubMed Central - PubMed

Affiliation: Inserm, UMR-S 945, Paris, France. michel.obeid@inserm.fr

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Dendritic cells mediate s.c.-primed immunityResults expressed as mean ± standard deviation (SD). All experiments were repeated three times (n = 3) with 3 to 5 mice per group at each time. * p = 0.0005 for (A), p = 0.023 for (B) and (C) by Kruskal–Wallis test with Dunn's post-test.BALB/c transgenic (CD11c-DTR) mice treated or not with DT to deplete DC, were immunized s.c. or i.d. with 200 × 103 265BY PyWT or γ-spz. The level of T-cell priming in the iLNs was then assessed through measurement of interferon-γ production after stimulation with a CS T-cell epitope.Assessment of the influence of DC depletion (by DT treatment, 2 days prior to each immunization) on the acquisition of sterile protection in BALB/c transgenic (CD11c-DTR) mice by s.c. immunization with two doses of 200 × 103 γ-spz at 1-weekly interval. The mice were challenged i.d. 1 week after the last s.c. immunization with 5 × 103 265BY PyWT, and protection defined as the absence of blood stages in Giemsa-stained blood smears collected from day 4 to day 14 post sporozoites infection.Adoptive transfer of cells purified from the iLN of BALB/c transgenic (CD11c-DTR) mice whose DC were depleted or not (DT or PBS treatment), prior to a single immunization with 600 × 103 γ-spz. The adoptively transferred cells were collected 5 days post-immunization and the recipient naïve mice were challenged 2 days later i.v. with 5 × 103 PyWT and the appearance of blood-stage parasites was monitored as above.
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fig03: Dendritic cells mediate s.c.-primed immunityResults expressed as mean ± standard deviation (SD). All experiments were repeated three times (n = 3) with 3 to 5 mice per group at each time. * p = 0.0005 for (A), p = 0.023 for (B) and (C) by Kruskal–Wallis test with Dunn's post-test.BALB/c transgenic (CD11c-DTR) mice treated or not with DT to deplete DC, were immunized s.c. or i.d. with 200 × 103 265BY PyWT or γ-spz. The level of T-cell priming in the iLNs was then assessed through measurement of interferon-γ production after stimulation with a CS T-cell epitope.Assessment of the influence of DC depletion (by DT treatment, 2 days prior to each immunization) on the acquisition of sterile protection in BALB/c transgenic (CD11c-DTR) mice by s.c. immunization with two doses of 200 × 103 γ-spz at 1-weekly interval. The mice were challenged i.d. 1 week after the last s.c. immunization with 5 × 103 265BY PyWT, and protection defined as the absence of blood stages in Giemsa-stained blood smears collected from day 4 to day 14 post sporozoites infection.Adoptive transfer of cells purified from the iLN of BALB/c transgenic (CD11c-DTR) mice whose DC were depleted or not (DT or PBS treatment), prior to a single immunization with 600 × 103 γ-spz. The adoptively transferred cells were collected 5 days post-immunization and the recipient naïve mice were challenged 2 days later i.v. with 5 × 103 PyWT and the appearance of blood-stage parasites was monitored as above.

Mentions: In order to minimize the circulation of activated T cells that is likely to occur with repeated boosting doses, we adopted an effective vaccination regimen of a single s.c. inoculation 600 × 103 γ-spz (Table 1). Groups of mice were immunized s.c. or i.d. with γ-spz, and one set was treated with DT whereas the other served as control. Cells from the iLN of control s.c.- or i.d.-immunized mice (i.e. not CD11c-depleted) produced high levels of interferon-γ in response to stimulus by a CSP epitope. In contrast, iLN cells from DT-injected immunized mice (i.e. CD11c DC-depleted) did not produce interferon-γ in response to the same stimulus (Fig 3A). Furthermore, the sterile protection conferred by immunization was completely abrogated by CD11c DC depletion (Fig 3B). Finally, adoptive transfer of iLN cells from control immunized mice protected recipient naïve mice against PyWT sporozoite challenge, but the iLN cells from CD11c DC-depleted immunized mice failed to do so (Fig 3C).


Skin-draining lymph node priming is sufficient to induce sterile immunity against pre-erythrocytic malaria.

Obeid M, Franetich JF, Lorthiois A, Gego A, Grüner AC, Tefit M, Boucheix C, Snounou G, Mazier D - EMBO Mol Med (2012)

Dendritic cells mediate s.c.-primed immunityResults expressed as mean ± standard deviation (SD). All experiments were repeated three times (n = 3) with 3 to 5 mice per group at each time. * p = 0.0005 for (A), p = 0.023 for (B) and (C) by Kruskal–Wallis test with Dunn's post-test.BALB/c transgenic (CD11c-DTR) mice treated or not with DT to deplete DC, were immunized s.c. or i.d. with 200 × 103 265BY PyWT or γ-spz. The level of T-cell priming in the iLNs was then assessed through measurement of interferon-γ production after stimulation with a CS T-cell epitope.Assessment of the influence of DC depletion (by DT treatment, 2 days prior to each immunization) on the acquisition of sterile protection in BALB/c transgenic (CD11c-DTR) mice by s.c. immunization with two doses of 200 × 103 γ-spz at 1-weekly interval. The mice were challenged i.d. 1 week after the last s.c. immunization with 5 × 103 265BY PyWT, and protection defined as the absence of blood stages in Giemsa-stained blood smears collected from day 4 to day 14 post sporozoites infection.Adoptive transfer of cells purified from the iLN of BALB/c transgenic (CD11c-DTR) mice whose DC were depleted or not (DT or PBS treatment), prior to a single immunization with 600 × 103 γ-spz. The adoptively transferred cells were collected 5 days post-immunization and the recipient naïve mice were challenged 2 days later i.v. with 5 × 103 PyWT and the appearance of blood-stage parasites was monitored as above.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3569641&req=5

fig03: Dendritic cells mediate s.c.-primed immunityResults expressed as mean ± standard deviation (SD). All experiments were repeated three times (n = 3) with 3 to 5 mice per group at each time. * p = 0.0005 for (A), p = 0.023 for (B) and (C) by Kruskal–Wallis test with Dunn's post-test.BALB/c transgenic (CD11c-DTR) mice treated or not with DT to deplete DC, were immunized s.c. or i.d. with 200 × 103 265BY PyWT or γ-spz. The level of T-cell priming in the iLNs was then assessed through measurement of interferon-γ production after stimulation with a CS T-cell epitope.Assessment of the influence of DC depletion (by DT treatment, 2 days prior to each immunization) on the acquisition of sterile protection in BALB/c transgenic (CD11c-DTR) mice by s.c. immunization with two doses of 200 × 103 γ-spz at 1-weekly interval. The mice were challenged i.d. 1 week after the last s.c. immunization with 5 × 103 265BY PyWT, and protection defined as the absence of blood stages in Giemsa-stained blood smears collected from day 4 to day 14 post sporozoites infection.Adoptive transfer of cells purified from the iLN of BALB/c transgenic (CD11c-DTR) mice whose DC were depleted or not (DT or PBS treatment), prior to a single immunization with 600 × 103 γ-spz. The adoptively transferred cells were collected 5 days post-immunization and the recipient naïve mice were challenged 2 days later i.v. with 5 × 103 PyWT and the appearance of blood-stage parasites was monitored as above.
Mentions: In order to minimize the circulation of activated T cells that is likely to occur with repeated boosting doses, we adopted an effective vaccination regimen of a single s.c. inoculation 600 × 103 γ-spz (Table 1). Groups of mice were immunized s.c. or i.d. with γ-spz, and one set was treated with DT whereas the other served as control. Cells from the iLN of control s.c.- or i.d.-immunized mice (i.e. not CD11c-depleted) produced high levels of interferon-γ in response to stimulus by a CSP epitope. In contrast, iLN cells from DT-injected immunized mice (i.e. CD11c DC-depleted) did not produce interferon-γ in response to the same stimulus (Fig 3A). Furthermore, the sterile protection conferred by immunization was completely abrogated by CD11c DC depletion (Fig 3B). Finally, adoptive transfer of iLN cells from control immunized mice protected recipient naïve mice against PyWT sporozoite challenge, but the iLN cells from CD11c DC-depleted immunized mice failed to do so (Fig 3C).

Bottom Line: However, it has recently been demonstrated that priming also occurs in the skin.We wished to establish if sterile protection could be obtained in the absence of priming by infected hepatocytes.We then compared and contrasted the patterns of priming with those obtained by intradermal immunization, where priming occurs in the liver.

View Article: PubMed Central - PubMed

Affiliation: Inserm, UMR-S 945, Paris, France. michel.obeid@inserm.fr

Show MeSH
Related in: MedlinePlus