Cytosolic expression of SecA2 is a prerequisite for long-term protective immunity.
Induction of efficient adaptive T cell-mediated immunity against the intracellular bacterium Listeria monocytogenes requires its successful invasion of host cell cytosol. However, it is not clear whether its cytosolic escape and growth are sufficient to induce T cell-mediated clearance and protection upon secondary infection. To investigate this issue, we have searched for mutants that do not induce long-term protective immunity yet invade the cytosol of infected cells. We found that mice immunized with L. monocytogenes lacking the SecA2 ATPase, an auxiliary protein secretion system present in several Gram-positive pathogenic bacteria, mounted a robust cytolytic IFN-gamma-secreting CD8+ T cell response but were not protected against a secondary challenge with wild-type (wt) bacteria. Furthermore, CD8+ T cells from mice immunized with secA2- bacteria failed to transfer protection when injected into recipient mice demonstrating that they were unable to confer protection. Also, secA2- and wt L. monocytogenes spread to the same myeloid-derived cell types in vivo and SecA2 deficiency does not interfere with intracytosolic bacteria multiplication. Therefore, cytosol invasion is not sufficient for inducing secondary protective responses and induction of memory CD8+ T cells mediating long-term antibacterial protective immunity is dependent upon SecA2 expression inside the cytosol of host cells in vivo.
Muraille
Eric
E
Institut National de la Santé et de la Recherche Médicale E03-44, Groupe Avenir, Institut de Pharmacologie Moléculaire et Cellulaire, 06560 Valbonne, France.
Narni-Mancinelli
Emilie
E
Gounon
Pierre
P
Bassand
Delphine
D
Glaichenhaus
Nicolas
N
Lenz
Laurel L
LL
Lauvau
Grégoire
G
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003600:Cytosol / Q000378:metabolism / Q000382:microbiology; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D013154:Spleen / Q000166:cytology / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D001426:Bacterial Proteins; D000251:Adenosine Triphosphatases