Open AccessSkin‐draining lymph node priming is sufficient to induce sterile immunity against pre‐erythrocytic malaria
Author(s) -
Obeid Michel,
Franetich JeanFrançois,
Lorthiois Audrey,
Gego Audrey,
Grüner Anne Charlotte,
Tefit Maurel,
Boucheix Claude,
Snounou Georges,
Mazier Dominique
Publication year - 2013
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201201677
Subject(s) - priming (agriculture) , plasmodium yoelii , biology , immunology , lymph node , immunity , lymph , immunization , vaccination , immune system , hepatocyte , virology , malaria , medicine , pathology , plasmodium falciparum , parasitemia , genetics , botany , germination , in vitro
Abstract The Plasmodium ‐infected hepatocyte has been considered necessary to prime the immune responses leading to sterile protection after vaccination with attenuated sporozoites. 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. To this end, we developed a subcutaneous (s.c.) immunization protocol where few, possibly none, of the immunizing irradiated Plasmodium yoelii sporozoites infect hepatocytes, and also used CD81‐deficient mice non‐permissive to productive hepatocyte infections. We then compared and contrasted the patterns of priming with those obtained by intradermal immunization, where priming occurs in the liver. Using sterile immunity as a primary read‐out, we exploited an inhibitor of T‐cell migration, transgenic mice with conditional depletion of dendritic cells and adoptive transfers of draining lymph node‐derived T cells, to provide evidence that responses leading to sterile immunity can be primed in the skin‐draining lymph nodes with little, if any, contribution from the infected hepatocyte.