Apoptosis of mouse dendritic cells is triggered by listeriolysin, the major virulence determinant of Listeria monocytogenes

CA Guzmán, E Domann, M Ronde… - Molecular …, 1996 - Wiley Online Library
CA Guzmán, E Domann, M Ronde, D Bruder, A Darji, S Weiss, J Wehland, T Chakraborty
Molecular microbiology, 1996Wiley Online Library
Infection of a murine‐spleen dendritic cell line by Listeria monocytogenes was found to
induce cell death through apoptosis. To characterize the bacterial product (s) involved in
induction of apoptosis, dendritic cells were infected with the L. monocytogenes EGD strain
and several isogenic mutants deficient in the production of individual listerial virulence
factors. The ability to induce cellular apoptosis was retained by all mutants tested, except the
prfA and Δhly mutants, both of which are unable to produce listeriolysin. Apoptosis was also …
Summary
Infection of a murine‐spleen dendritic cell line by Listeria monocytogenes was found to induce cell death through apoptosis. To characterize the bacterial product(s) involved in induction of apoptosis, dendritic cells were infected with the L. monocytogenes EGD strain and several isogenic mutants deficient in the production of individual listerial virulence factors. The ability to induce cellular apoptosis was retained by all mutants tested, except the prfA and Δhly mutants, both of which are unable to produce listeriolysin. Apoptosis was also induced by purified listeriolysin suggesting that this protein directly induces apoptosis. Purified recombinant listeriolysins rendered either weakly haemolytic by a C‐484 to S mutation, or non‐haemolytic by a W‐491 to A mutation exhibited little or no capacity to induce apoptosis, indicating that both activities are associated within the same protein region. Treatment with purified listeriolysin or L. monocytogenes infection also triggers apoptosis in explanted bone‐marrow dendritic cells. Thus invasion of dendritic cells by L. monocytogenes, which results in cell death, may play an important role in the pathogenesis of listerial infections by impairing immune responses, hindering bacterial clearance and promoting spread of the infection.
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