TY - JOUR
T1 - Leishmania disease development depends on the presence of apoptotic promastigotes in the virulent inoculum
AU - Van Zandbergen, Ger
AU - Bollinger, Annalena
AU - Wenzel, Alexander
AU - Kamhawi, Shaden
AU - Voll, Reinhard
AU - Klinger, Matthias
AU - Müller, Antje
AU - Hölscher, Christoph
AU - Herrmann, Martin
AU - Sacks, David
AU - Solbach, Werner
AU - Laskay, Tamás
PY - 2006/9/12
Y1 - 2006/9/12
N2 - The obligate intracellular pathogen Leishmania major survives and multiplies in professional phagocytes. The evasion strategy to circumvent killing by host phagocytes and establish a productive infection is poorly understood. Here we report that the virulent inoculum of Leishmania promastigotes contains a high ratio of annexin A5-binding apoptotic parasites. This subpopulation of parasites is characterized by a round body shape, a swollen kinetoplast, nuclear condensation, and a lack of multiplication and represents dying or already dead parasites. After depleting the apoptotic parasites from a virulent population, Leishmania do not survive in phagocytes in vitro and lose their disease-inducing ability in vivo. TGF-β induced by apoptotic parasites is likely to mediate the silencing of phagocytes and lead to survival of infectious Leishmania populations. The data demonstrate that apoptotic promastigotes, in an altruistic way, enable the intracellular survival of the viable parasites.
AB - The obligate intracellular pathogen Leishmania major survives and multiplies in professional phagocytes. The evasion strategy to circumvent killing by host phagocytes and establish a productive infection is poorly understood. Here we report that the virulent inoculum of Leishmania promastigotes contains a high ratio of annexin A5-binding apoptotic parasites. This subpopulation of parasites is characterized by a round body shape, a swollen kinetoplast, nuclear condensation, and a lack of multiplication and represents dying or already dead parasites. After depleting the apoptotic parasites from a virulent population, Leishmania do not survive in phagocytes in vitro and lose their disease-inducing ability in vivo. TGF-β induced by apoptotic parasites is likely to mediate the silencing of phagocytes and lead to survival of infectious Leishmania populations. The data demonstrate that apoptotic promastigotes, in an altruistic way, enable the intracellular survival of the viable parasites.
UR - http://www.scopus.com/inward/record.url?scp=33748808057&partnerID=8YFLogxK
U2 - 10.1073/pnas.0600843103
DO - 10.1073/pnas.0600843103
M3 - Journal articles
C2 - 16945916
AN - SCOPUS:33748808057
SN - 0027-8424
VL - 103
SP - 13837
EP - 13842
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 37
ER -