scholarly journals Leishmania amazonensis hijacks host cell lysosomes involved in plasma membrane repair to induce invasion in fibroblasts

2019 ◽  
Vol 132 (6) ◽  
pp. jcs226183 ◽  
Author(s):  
Victor Soares Cavalcante-Costa ◽  
Mariana Costa-Reginaldo ◽  
Thamires Queiroz-Oliveira ◽  
Anny C. S. Oliveira ◽  
Natália Fernanda Couto ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Host Cell ◽  
Leishmania Amazonensis ◽  
Membrane Repair ◽  
Plasma Membrane Repair

scholarly journals LAMP-2 absence interferes with plasma membrane repair and decreases T. cruzi host cell invasion

2017 ◽  
Vol 11 (6) ◽  
pp. e0005657 ◽  
Author(s):  
Natália Fernanda Couto ◽  
Dina Pedersane ◽  
Luisa Rezende ◽  
Patrícia P. Dias ◽  
Tayanne L. Corbani ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Host Cell ◽  
Cell Invasion ◽  
Host Cell Invasion ◽  
Membrane Repair ◽  
Plasma Membrane Repair

scholarly journals Correction: LAMP-2 absence interferes with plasma membrane repair and decreases T. cruzi host cell invasion

2020 ◽  
Vol 14 (9) ◽  
pp. e0008724
Author(s):  
Natália Fernanda do Couto ◽  
Dina Pedersane ◽  
Luisa Rezende ◽  
Patrícia P. Dias ◽  
Tayanne L. Corbani ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Host Cell ◽  
Cell Invasion ◽  
Host Cell Invasion ◽  
Membrane Repair ◽  
Plasma Membrane Repair

scholarly journals Unveiling Leishmania invasion of fibroblasts: calcium signaling, lysosome recruitment and exocytosis culminate with actin-independent invasion

2018 ◽  
Author(s):  
Victor Soares Cavalcante-Costa ◽  
Mariana Costa-Reginaldo ◽  
Thamires Queiroz-Oliveira ◽  
Anny Carolline Silva Oliveira ◽  
Natália Fernanda Couto ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Calcium Signaling ◽  
Host Cell ◽  
Insect Vector ◽  
Membrane Repair ◽  
Phagocytic Cells ◽  
Intracellular Parasites ◽  
Leishmania Spp ◽  
Causative Agents ◽  
Plasma Membrane Repair

ABSTRACTIntracellular parasites of the genus Leishmania are the causative agents of human leishmaniasis, a widespread emergent tropical disease. The parasite is transmitted by the bite of a hematophagous sandfly vector that inoculates motile flagellated promastigote forms into the dermis of the mammalian host. After inoculation, parasites are ultimately captured by macrophages and multiply as round-shaped amastigote forms. Macrophages seem not to be the first infected cells since parasites were observed invading neutrophils first whose leishmania-containing apoptotic bodies were latter captured by macrophages, thereby becoming infected. The fact that Leishmania spp are able to live and replicate inside immune phagocytic cells and that macrophages are the main cell type found infected in chronicity created the perception that Leishmania spp are passive players waiting to be captured by phagocytes. However, several groups have described the infection of non-phagocytic cells in vivo and in vitro. The objective of this work was to study the cellular mechanisms involved in the invasion of non-professional phagocytes by Leishmania. We show that promastigotes of L.amazonensis actively induces invasion in fibroblasts without cytoskeleton activity, thus by a mechanism that is distinct from phagocytosis. Inside fibroblasts parasites transformed in amastigotes, remained viable for at least two weeks and re-transformed in promastigotes when returned to insect vector conditions. Similarly to what was observed for T. cruzi, infection involves calcium signaling, recruitment and exocytosis of lysosomes involved in plasma membrane repair and lysosome-triggered endocytosis. Conditions that alter lysosomal function such as cytochalasin-D and brefeldin-A treatment or the knockout of host cell lysosomal proteins LAMP-1 and 2 dramatically affected invasion. Likewise, triggering of lysosomal exocytosis and lysosome-dependent plasma membrane repair by low doses of streptolysin-O dramatically increased parasite entry. Together our results show that L.amazonensis promastigotes are able to take advantage of calcium-dependent lysosomal exocytosis and lysosome-induced endocytosis to invade and persist in non-phagocytic cells.AUTHOR SUMMARYIntracellular parasites of the genus Leishmania are the causative agents of leishmaniasis. The disease is transmitted by the bite of a sand fly vector which inoculates the parasite into the skin of mammalian hosts, including humans. During chronic infection the parasite lives and replicates inside phagocytic cells, notably the macrophages. An interesting but overlooked finding on Leishmania infection is that non-phagocytic cells have also been found infected by amastigotes. Nevertheless, the mechanisms by which Leishmania invades non-phagocytic cells were not studied to date. Here we show that L. amazonensis can actively induce their own entry into fibroblasts independently of actin cytoskeleton activity, thus by a mechanism that is distinct from phagocytosis. Invasion involves subversion of host cell functions such as calcium signaling and recruitment and exocytosis of host cell lysosomes involved in plasma membrane repair and whose positioning and content interfere in invasion. Parasites were able to replicate and remained viable in fibroblasts, suggesting that cell invasion trough the mechanism demonstrated here could serve as a parasite hideout and reservoir, facilitating infection amplification and persistence.

scholarly journals Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion

2011 ◽  
Vol 208 (5) ◽  
pp. 909-921 ◽  
Author(s):  
Maria Cecilia Fernandes ◽  
Mauro Cortez ◽  
Andrew R. Flannery ◽  
Christina Tam ◽  
Renato A. Mortara ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Cell Invasion ◽  
Acid Sphingomyelinase ◽  
Host Cells ◽  
Cell Contact ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Plasma Membrane Repair

Upon host cell contact, the protozoan parasite Trypanosoma cruzi triggers cytosolic Ca2+ transients that induce exocytosis of lysosomes, a process required for cell invasion. However, the exact mechanism by which lysosomal exocytosis mediates T. cruzi internalization remains unclear. We show that host cell entry by T. cruzi mimics a process of plasma membrane injury and repair that involves Ca2+-dependent exocytosis of lysosomes, delivery of acid sphingomyelinase (ASM) to the outer leaflet of the plasma membrane, and a rapid form of endocytosis that internalizes membrane lesions. Host cells incubated with T. cruzi trypomastigotes are transiently wounded, show increased levels of endocytosis, and become more susceptible to infection when injured with pore-forming toxins. Inhibition or depletion of lysosomal ASM, which blocks plasma membrane repair, markedly reduces the susceptibility of host cells to T. cruzi invasion. Notably, extracellular addition of sphingomyelinase stimulates host cell endocytosis, enhances T. cruzi invasion, and restores normal invasion levels in ASM-depleted cells. Ceramide, the product of sphingomyelin hydrolysis, is detected in newly formed parasitophorous vacuoles containing trypomastigotes but not in the few parasite-containing vacuoles formed in ASM-depleted cells. Thus, T. cruzi subverts the ASM-dependent ceramide-enriched endosomes that function in plasma membrane repair to infect host cells.

scholarly journals Plasma membrane repairs by small GTPase Rab3a

2016 ◽  
Vol 213 (6) ◽  
pp. 613-615 ◽  
Author(s):  
Camilla Raiborg ◽  
Harald Stenmark
Keyword(s):  
Plasma Membrane ◽  
Small Gtpase ◽  
Membrane Repair ◽  
Cell Biol ◽  
Plasma Membrane Repair

Lysosomes fuse with the plasma membrane to help repair membrane lesions, but how they are positioned close to these lesions is not fully understood. Now, Encarnação et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201511093) demonstrate that the lysosomal GTPase Rab3a and its effectors orchestrate lysosome positioning and plasma membrane repair.

scholarly journals Mitochondrial fragmentation enables localized signaling required for cell repair

2020 ◽  
Vol 219 (5) ◽  
Author(s):  
Adam Horn ◽  
Shreya Raavicharla ◽  
Sonna Shah ◽  
Dan Cox ◽  
Jyoti K. Jaiswal
Keyword(s):  
Plasma Membrane ◽  
Calcium Influx ◽  
Cell Damage ◽  
Mitochondrial Fission ◽  
Adaptor Protein ◽  
Mitochondrial Fragmentation ◽  
Membrane Repair ◽  
Membrane Injury ◽  
Mitochondrial Signaling ◽  
Plasma Membrane Repair

Plasma membrane injury can cause lethal influx of calcium, but cells survive by mounting a polarized repair response targeted to the wound site. Mitochondrial signaling within seconds after injury enables this response. However, as mitochondria are distributed throughout the cell in an interconnected network, it is unclear how they generate a spatially restricted signal to repair the plasma membrane wound. Here we show that calcium influx and Drp1-mediated, rapid mitochondrial fission at the injury site help polarize the repair response. Fission of injury-proximal mitochondria allows for greater amplitude and duration of calcium increase in these mitochondria, allowing them to generate local redox signaling required for plasma membrane repair. Drp1 knockout cells and patient cells lacking the Drp1 adaptor protein MiD49 fail to undergo injury-triggered mitochondrial fission, preventing polarized mitochondrial calcium increase and plasma membrane repair. Although mitochondrial fission is considered to be an indicator of cell damage and death, our findings identify that mitochondrial fission generates localized signaling required for cell survival.

scholarly journals Annexin A7 is required for ESCRT III-mediated plasma membrane repair

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Stine Lauritzen Sønder ◽  
Theresa Louise Boye ◽  
Regine Tölle ◽  
Jörn Dengjel ◽  
Kenji Maeda ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Repair ◽  
Plasma Membrane Repair ◽  
Annexin A7

Plasma membrane repair and cellular damage control: The annexin survival kit

2011 ◽  
Vol 81 (6) ◽  
pp. 703-712 ◽  
Author(s):  
Annette Draeger ◽  
Katia Monastyrskaya ◽  
Eduard B. Babiychuk
Keyword(s):  
Plasma Membrane ◽  
Damage Control ◽  
Cellular Damage ◽  
Membrane Repair ◽  
Plasma Membrane Repair
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