Skin-draining lymph node priming is sufficient to induce sterile immunity against pre-erythrocytic malaria.
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.
Affiliation: Inserm, UMR-S 945, Paris, France. email@example.comShow MeSH
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Mentions: It is possible that some of s.c.-inoculated attenuated sporozoites escape the skin and reach the liver, where they, or antigens derived from them, would also induce immune responses leading to sterile protection. Therefore, we used a sensitive amplification protocol to establish whether parasites could be detected in the spleens or livers of mice inoculated with 100 × 103 γ-spz i.d., or with a substantially larger dose (250 × 103) s.c. The spleens and livers of some experimental animals were harvested 4 or 40 h post-inoculation, respectively. In other s.c. inoculated animals, the spleens and livers were harvested at 1, 6, 12 and 40 h post-inoculation. Total RNA was isolated from these livers and spleens and used in an RT-nested PCR assay to detect small amounts of the parasite's small subunit ribosomal RNA gene. No amplification product was obtained in any of the liver or spleen samples collected from mice inoculated s.c. (Fig 1B), in contrast to robust amplification in the samples collected from i.d.- and i.v.-inoculated mice (Fig 1A). The sensitivity of the method is attested by the positive results observed for the liver samples obtained from mice inoculated i.v. with only 500 γ-spz (assuming most of the sporozoites invaded hepatocytes and that each parasite harbours a conservative 500 ribosomes, the aliquot assayed would correspond to about 150 target copies). Thus, it is likely that none, or substantially <0.2% of the 250 × 103 γ-spz inoculated s.c. would have reached, or persisted in, the liver. Given that an i.v. immunization schedule based on 500 γ-spz does not lead to sterile protection against normal challenge, a minute proportion of the s.c.-inoculated γ-spz that might have made their way out of the skin to liver would not account for the protective immunity we obtained in our model.
Affiliation: Inserm, UMR-S 945, Paris, France. firstname.lastname@example.org