The role of apoptotic mimicry in host-parasite interplay: is death the only alternative for altruistic behavior?

Barcinski, Marcello A.; Moreira, M E C; Balanco, José Mario de Freitas; Wanderley, João Luiz Mendes; Bonomo, Adriana

doi:10.1186/1475-9292-2-6

Cited by 13 publications

(8 citation statements)

References 11 publications

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“…The role of the apoptosis-like PS exposure in the establishment of a Leishmania infection has been widely discussed. One possibility in this respect is that PS-positive cells do not necessarily die but use PS exposure, in an apoptosis-mimicking fashion, to infect macrophages and inhibit their microbicidal activity [8], [11], [16], [65]. The second possibility suggests that PS-positive forms are indeed “altruistic” apoptotic parasites that have been sentenced to death but are nevertheless required in order that the PS-negative infective parasites invade the host cell, in a truly cooperative system [16], [66].…”

Section: Discussionmentioning

confidence: 99%

“…In our case, the experiments were performed using early stationary phase Leishmania parasites, where rounded apoptotic forms were not detected. In any case, PS exposure is the relevant phenotype for macrophages infection and subsequent inactivation of microbicidal activity in both these scenarios, thereby allowing parasite persistence in the host [65].…”

Section: Discussionmentioning

confidence: 99%

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LABCG2, a New ABC Transporter Implicated in Phosphatidylserine Exposure, Is Involved in the Infectivity and Pathogenicity of Leishmania

et al. 2013

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Leishmaniasis is a neglected disease produced by the intracellular protozoan parasite Leishmania. In the present study, we show that LABCG2, a new ATP-binding cassette half-transporter (ABCG subfamily) from Leishmania, is involved in parasite virulence. Down-regulation of LABCG2 function upon expression of an inactive mutant version of this half-transporter (LABCG2K/M) is shown to reduce the translocation of short-chain analogues of phosphatidylserine (PS). This dominant-negative phenotype is specific for the headgroup of the phospholipid, as the movement of phospholipid analogues of phosphatidylcholine, phosphatidylethanolamine or sphingomyelin is not affected. In addition, promastigotes expressing LABCG2K/M expose less endogenous PS in the stationary phase than control parasites. Transient exposure of PS at the outer leaflet of the plasma membrane is known to be one of the mechanisms used by Leishmania to infect macrophages and to silence their immune response. Stationary phase/metacyclic promastigotes expressing LABCG2K/M are less infective for macrophages and show decreased pathogenesis in a mouse model of cutaneous leishmaniasis. Thus, mice infected with parasites expressing LABCG2K/M did not develop any lesion and showed significantly lower inflammation and parasite burden than mice infected with control parasites. Our results indicate that LABCG2 function is required for the externalization of PS in Leishmania promastigotes, a process that is involved in the virulence of the parasite.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LABCG2, a New ABC Transporter Implicated in Phosphatidylserine Exposure, Is Involved in the Infectivity and Pathogenicity of Leishmania

et al. 2013

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“…These factors favor the entry and multiplication of parasites in macrophages. It has also been proven that PS is a potent stimulator of apoptosis (BARCINSKI et al, 2003). Experimental infection by Leishmania donovani has been shown to induce apoptosis of immune system cells that are not infected (CD4 T lymphocytes), possibly due to the influence of the lipophosphoglycan (LPG) that is present in its cell wall (LÜDER et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Influence of apoptosis on liver and spleen resistance in dogs with visceral leishmaniosis

Moreira

Franciscato

Rossit

et al. 2016

Rev. Bras. Parasitol. Vet.

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The aim of this study was to evaluate apoptosis and parasite load in the liver and spleen of dogs with visceral leishmaniosis (VL), using immunohistochemistry. Liver and spleen samples from 71 dogs with VL were used. The parasite load in the spleen and liver showed significant difference between organs in infected group (P=0.0219). The density of the parasite load in the spleen (median=2.4) was higher than liver (median=0.8). Immunodetection of apoptotic cells was predominant in lymphocytes and differ between the infected and control group in spleen (P=0.0307) and liver (P=0.0346). There was a significant correlation between apoptosis and parasite load (P = 0.0084; r=0.3104) only in the spleen of the infected group, where it was observed that, when increasing the number of apoptotic cells increases the parasitic load. It was concluded that the liver and spleen of infected dogs presented greater numbers of cells undergoing apoptosis (lymphocytes) than the control group, thus suggesting that this process may be contributing towards the survival of Leishmania in these organs, because lymphocyte in apoptosis did not have the ability to present and recognize the antigen, allowing the survival of the parasite.Keywords: Leishmania infantum, immune escape, apoptosis, dogs. ResumoO objetivo deste estudo foi avaliar a apoptose e a carga parasitária no fígado e baço de cães com leishmaniose visceral (LV), pela técnica de imuno-histoquímica. Foram utilizadas amostras de fígado e baço de 71 cães com LV. A carga parasitária no baço e fígado mostrou diferença significativa entre os órgãos no grupo infectado (P=0,0219). A densidade da carga de parasita no baço (média=2,4) foi maior do que no fígado (média=0,8). A imunodetecção de células em apoptose foi predominante nos linfócitos, com diferenças entre o grupo infectado e controle no baço (P=0,0307) e fígado (P=0,0346). Houve uma correlação positiva fraca entre apoptose e carga parasitária (P=0,0084; r=0,3104) apenas no baço do grupo infectado, onde observou-se que quando aumentava o número de células em apoptose aumentava a carga parasitária. Concluiu-se que o fígado e o baço de cães infectados apresentam um maior número de células que sofrem apoptose (linfócitos) do que o grupo controle, sugerindo que este processo possa contribuir para a sobrevivência de Leishmania nestes órgãos, pois os linfócitos em apoptose não tiveram a capacidade de apresentar e reconhecer o antígeno, permitindo a sobrevivência do parasita.Palavras-chave: Leishmania infantum, evasão da resposta imune, apoptose, cães.

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“…Phagocytosis of apoptotic cells by macrophages induces a noninflammatory response based on the exposure of PS [11] that leads to TGF-b1 secretion [11] , [12] . Due to this property, PS has been related to the evasion mechanism of Leishmania amazonensis from macrophages, a concept known as “apoptotic mimicry” [13] , [14] . It was demonstrated that this protozoan exposes PS and this is involved in the internalization process, causing alternative activation of macrophage through the induction of TGF-b1 secretion, interleukin (IL)-10 synthesis, and inhibition of NO production [15] , [16] .…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylserine Exposure by Toxoplasma gondii Is Fundamental to Balance the Immune Response Granting Survival of the Parasite and of the Host

et al. 2011

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Phosphatidylserine (PS) exposure on the cell surface indicates apoptosis, but has also been related to evasion mechanisms of parasites, a concept known as apoptotic mimicry. Toxoplasma gondii mimics apoptotic cells by exposing PS, inducing secretion of TGF-beta1 by infected activated macrophages leading to degradation of inducible nitric oxide (NO) synthase, NO production inhibition and consequently persisting in these cells. Here PS+ and PS− subpopulation of tachyzoites were separated and the entrance mechanism, growth and NO inhibition in murine macrophages, and mice survival and pathology were analyzed. Infection index in resident macrophages was similar for both PS subpopulations but lower when compared to the total T. gondii population. Growth in resident macrophages was higher for the total T. gondii population, intermediate for the PS+ and lower for the PS− subpopulation. Production of NO by activated macrophages was inhibited after infection with the PS+ subpopulation and the total populations of tachyzoites. However, the PS− subpopulation was not able to inhibit NO production. PS+ subpopulation invaded macrophages by active penetration as indicated by tight-fitting vacuoles, but the PS− subpopulation entered macrophages by phagocytosis as suggested by loose-fitting vacuoles containing these tachyzoites. The entrance mechanism of both subpopulations was confirmed in a non-professional phagocytic cell line where only the PS+ tachyzoites were found inside these cells in tight-fitting vacuoles. Both subpopulations of T. gondii killed mice faster than the total population. Clear signs of inflammation and no tachyzoites were seen in the peritoneal cavity of mice infected with the PS− subpopulation. Moreover, mice infected with the PS+ subpopulation had no sign of inflammation and the parasite burden was intense. These results show that PS+ and PS− subpopulations of T. gondii are necessary for a successful toxoplasma infection indicating that both subpopulations are required to maintain the balance between inflammation and parasite growth.

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The role of apoptotic mimicry in host-parasite interplay: is death the only alternative for altruistic behavior?

Cited by 13 publications

References 11 publications

LABCG2, a New ABC Transporter Implicated in Phosphatidylserine Exposure, Is Involved in the Infectivity and Pathogenicity of Leishmania

LABCG2, a New ABC Transporter Implicated in Phosphatidylserine Exposure, Is Involved in the Infectivity and Pathogenicity of Leishmania

Influence of apoptosis on liver and spleen resistance in dogs with visceral leishmaniosis

Phosphatidylserine Exposure by Toxoplasma gondii Is Fundamental to Balance the Immune Response Granting Survival of the Parasite and of the Host

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