TY - JOUR
T1 - Cytosolic expression of SecA2 is a prerequisite for long-term protective immunity
AU - Muraille, Eric
AU - Narni-mancinelli, Emilie
AU - Gounon, Pierre
AU - Bassand, Delphine
AU - Glaichenhaus, Nicolas
AU - Lenz, Laurel L.
AU - Lauvau, Grégoire
PY - 2007/6
Y1 - 2007/6
N2 - 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-γ-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.
AB - 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-γ-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.
UR - http://www.scopus.com/inward/record.url?scp=34248636516&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34248636516&partnerID=8YFLogxK
U2 - 10.1111/j.1462-5822.2007.00883.x
DO - 10.1111/j.1462-5822.2007.00883.x
M3 - Article
C2 - 17244189
AN - SCOPUS:34248636516
SN - 1462-5814
VL - 9
SP - 1445
EP - 1454
JO - Cellular Microbiology
JF - Cellular Microbiology
IS - 6
ER -