Apoptosis in parasites and parasite-induced apoptosis in the host immune system: a new approach to parasitic diseases

Barcinski, Marcello A.; DosReis, George A.

doi:10.1590/s0100-879x1999000400003

Cited by 66 publications

(35 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As Leishmania parasites are transferred by the sandfly, apoptosis-like cell death could serve to restrict population growth in the vector, hereby increasing the life span of the vector and increasing the transmission rate, as shown for other protozoan parasites. 3,4 From another point of view it is also tempted to speculate that the presence of apoptotic-like parasites has an immune-silencing effect, as has been shown upon apoptotic cell clearance during homeostasis. Santos et al already showed that phosphatidylserine exposure by Toxoplasma gondii is fundamental for granting survival of the parasite in murine macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…As most protozoan parasites are vector transmitted, it may be necessary to restrict the population size in the vector, as shown for Trypanosoma brucei and Plasmodium. 3,4 From an overall population perspective, the induction of apoptosis could also be employed by the parasites to evade early immune responses. Evidence supporting the idea that apoptosis contributes to survival of the overall population was given by the fact that phagocytosis of apoptotic-like parasites induces production of anti-inflammatory mediators, likely to silence phagocytes enabling the intracellular survival of viable parasites.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Apoptotic-likeLeishmaniaexploit the host´s autophagy machinery to reduce T-cell-mediated parasite elimination

et al. 2015

View full text Add to dashboard Cite

Apoptosis is a well-defined cellular process in which a cell dies, characterized by cell shrinkage and DNA fragmentation. In parasites like Leishmania, the process of apoptosis-like cell death has been described. Moreover upon infection, the apoptotic-like population is essential for disease development, in part by silencing host phagocytes. Nevertheless, the exact mechanism of how apoptosis in unicellular organisms may support infectivity remains unclear. Therefore we investigated the fate of apoptotic-like Leishmania parasites in human host macrophages. Our data showed-in contrast to viable parasites-that apoptotic-like parasites enter an LC3 C , autophagy-like compartment. The compartment was found to consist of a single lipid bilayer, typical for LC3-associated phagocytosis (LAP). As LAP can provoke anti-inflammatory responses and autophagy modulates antigen presentation, we analyzed how the presence of apoptotic-like parasites affected the adaptive immune response. Macrophages infected with viable Leishmania induced proliferation of CD4 C T-cells, leading to a reduced intracellular parasite survival. Remarkably, the presence of apoptotic-like parasites in the inoculum significantly reduced T-cell proliferation. Chemical induction of autophagy in human monocyte-derived macrophage (hMDM), infected with viable parasites only, had an even stronger proliferationreducing effect, indicating that host cell autophagy and not parasite viability limits the T-cell response and enhances parasite survival. Concluding, our data suggest that apoptotic-like Leishmania hijack the host cells´autophagy machinery to reduce T-cell proliferation. Furthermore, the overall population survival is guaranteed, explaining the benefit of apoptosis-like cell death in a single-celled parasite and defining the host autophagy pathway as a potential therapeutic target in treating Leishmaniasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Apoptotic-likeLeishmaniaexploit the host´s autophagy machinery to reduce T-cell-mediated parasite elimination

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Cell death of lymphocytes is necessary to preserve a healthy and balanced immune system [35]. Nevertheless, if during an infectious process lymphocyte apoptosis occurs prior to pathogen elimination, it could restrict the magnitude of the effector response [36], especially if the apoptosis occurs at early stages of lymphocyte development. Thus, immature B cell reduction during an infection would limit antibody production and favor parasite replication and chronicity; so the identification of the mechanisms ruling lymphocyte apoptosis represents a current and major challenge in biomedical research.…”

Section: Discussionmentioning

confidence: 99%

Depletion of immature B cells duringTrypanosoma cruzi infection: involvement of myeloid cells and the cyclooxygenase pathway

et al. 2005

View full text Add to dashboard Cite

The ability of a microorganism to elicit or evade B cell responses represents a determinant factor for the final outcome of an infection. Although pathogens may subvert humoral responses at different stages of B cell development, most studies addressing the impact of an infection on the B cell compartment have focused on mature B cells within peripheral lymphoid organs. Herein, we report that a protozoan infection, i.e. a Trypanosoma cruzi infection, induces a marked loss of immature B cells in the BM, which also compromises recently emigrated B cells in the periphery. The depletion of BM immature B cells is associated with an increased rate of apoptosis mediated by a parasite-indirect mechanism in a Fas/FasL-independent fashion. Finally, we demonstrated that myeloid cells play an important role in B cell depletion, since CD11b + BM cells from infected mice secrete a product of the cyclooxygenase pathway that eliminates immature B cells. These results highlight a previously unrecognized maneuver used by a protozoan parasite to disable B cell generation, limiting host defense and favoring its chronic establishment.

show abstract

“…This phenomenon plays an important role in the immunopathogenesis of several parasitic diseases (27,28). Studies on cell death in protozoonoses have also focused on its possible role in the immunopathology of experimental Chagas disease (29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Detection of early apoptosis and cell death in T CD4+ and CD8+ cells from lesions of patients with localized cutaneous leishmaniasis

Bertho

Santiago

Da‐Cruz

et al. 2000

Braz J Med Biol Res

View full text Add to dashboard Cite

Human localized cutaneous leishmaniasis (LCL), induced by Leishmania braziliensis, ranges from a clinically mild, self-healing disease with localized cutaneous lesions to severe forms which can present secondary metastatic lesions. The T cell-mediated immune response is extremely important to define the outcome of the disease; however, the underlying mechanisms involved are not fully understood. A flow cytometric analysis of incorporation of 7-amino actinomycin D and CD4 + or CD8 + T cell surface phenotyping was used to determine whether different frequencies of early apoptosis or accidental cell death occur at different stages of LCL lesions. When all cells obtained from a biopsy sample were analyzed, larger numbers of early apoptotic and dead cells were observed in lesions from patients with active disease (mean = 39.5 ± 2.7%) as compared with lesions undergoing spontaneous healing (mean = 17.8 ± 2.2%). Cells displaying normal viability patterns obtained from active LCL lesions showed higher numbers of early apoptotic events among CD8 + than among CD4 + T cells (mean = 28.5 ± 3.8 and 15.3 ± 3.0%, respectively). The higher frequency of cell death events in CD8 + T cells from patients with LCL may be associated with an active form of the disease. In addition, low frequencies of early apoptotic events among the CD8 + T cells were observed in two patients with self-healing lesions. Although the number of patients in the latter group was small, it is possible to speculate that, during the immune response, differences in apoptotic events in CD4 + and CD8 + T cell subsets could be responsible for controlling the CD4/CD8 ratio, thus leading to healing or maintenance of disease. Correspondence

show abstract

Apoptosis in parasites and parasite-induced apoptosis in the host immune system: a new approach to parasitic diseases

Cited by 66 publications

References 42 publications

Apoptotic-likeLeishmaniaexploit the host´s autophagy machinery to reduce T-cell-mediated parasite elimination

Apoptotic-likeLeishmaniaexploit the host´s autophagy machinery to reduce T-cell-mediated parasite elimination

Depletion of immature B cells duringTrypanosoma cruzi infection: involvement of myeloid cells and the cyclooxygenase pathway

Detection of early apoptosis and cell death in T CD4+ and CD8+ cells from lesions of patients with localized cutaneous leishmaniasis

Contact Info

Product

Resources

About