Merozoites Obtained through a Simpler Method Do Not Survive in Classically Activated Macrophages.

Malaria is caused by apicomplexan parasites of the genus. is an excellent animal model for the study of human malaria caused by . Merozoites invade erythrocytes but are also found in other host cells including macrophages from the spleen and liver.

Mature Naive B Cells Regulate the Outcome of Murine Acute Graft-versus-Host Disease in an IL-10-Independent Manner.

Graft-versus-host disease (GVHD) is the main complication of bone marrow transplantation (BMT). CD4 T lymphocytes are the main effector cells for disease development, but other cell types can determine disease outcome through cytokine production and antigen presentation. B cells are abundant in BMT products and are involved in chronic GVHD immunopathogenesis.

Apoptotic mimicry as a strategy for the establishment of parasitic infections: parasite- and host-derived phosphatidylserine as key molecule.

The establishment of parasitic infection is dependent on the development of efficient strategies to evade the host defense mechanisms. Phosphatidylserine (PS) molecules are pivotal for apoptotic cell recognition and clearance by professional phagocytes. Moreover, PS receptors are able to trigger anti-inflammatory and immunosuppressive responses by phagocytes, either by coupled enzymes or through the induction of regulatory cytokine secretion.

CD4 T Cell-Dependent Macrophage Activation Modulates Sustained PS Exposure on Intracellular Amastigotes of .

amastigotes can make use of surface-exposed phosphatidylserine (PS) molecules to promote infection and non-classical activation of macrophages (MΦ), leading to uncontrolled intracellular proliferation of the parasites. This mechanism was quoted as apoptotic mimicry. Moreover, the amount of PS molecules exposed on the surface of amastigotes correlates with the susceptibility of the host.

Leishmaniasis and glycosaminoglycans: a future therapeutic strategy?

Leishmania spp. depend on effective macrophage infection to establish and develop in mammalian hosts. Both metacyclic promastigotes and amastigotes are able to infect host cells, and thus they rely on several ligands that, when recognized by macrophage receptors, mediate parasite uptake.

Disease severity and mortality can be independently regulated in a mouse model of experimental graft versus host disease.

Graft versus host disease (GVHD) is the major limitation of allogeneic hematopoietic stem cell transplantation (HSCT) presenting high mortality and morbidity rates. However, the exact cause of death is not completely understood and does not correlate with specific clinical and histological parameters of disease. Here we show, by using a semi-allogeneic mouse model of GVHD, that mortality and morbidity can be experimentally separated.

Apoptosis and apoptotic mimicry in Leishmania: an evolutionary perspective.

Apoptotic death and apoptotic mimicry are defined respectively as a non-accidental death and as the mimicking of an apoptotic-cell phenotype, usually by phosphatidylserine (PS) exposure. In the case of the murine infection by Leishmania spp, apoptotic death has been described in promastigotes and apoptotic mimicry in amastigotes. In both situations they are important events of the experimental murine infection by this parasite.

Exposure of phosphatidylserine on Leishmania amazonensis isolates is associated with diffuse cutaneous leishmaniasis and parasite infectivity.

Diffuse cutaneous leishmaniasis (DCL) is a rare clinical manifestation of leishmaniasis, characterized by an inefficient parasite-specific cellular response and heavily parasitized macrophages. In Brazil, Leishmania (Leishmania) amazonensis is the main species involved in DCL cases. In the experimental model, recognition of phosphatidylserine (PS) molecules exposed on the surface of amastigotes forms of L.

Blockade of irradiation-induced autophagosome formation impairs proliferation but does not enhance cell death in HCT-116 human colorectal carcinoma cells.

This work was undertaken to gain further information on the molecular mechanisms underlying autophagosome formation and its relation with tumor cell survival in response to radiation in colon cancer. A human colon cancer cell line, HCT-116, was examined with respect to cell survival after blockade of irradiation-induced autophagosome formation by pharmacological interference. Autophagosome formation was confirmed using a kinetic study with incorporated bovine serum albumin gold-conjugate (BSA-Au) analyzed by electron microscopy and an autophagosome-associated LC3B antibody measured by immunofluorescence and Western blotting.

Osteopontin-c splicing isoform contributes to ovarian cancer progression.

Ovarian carcinoma is one of the most aggressive gynecological diseases and generally diagnosed at advanced stages. Osteopontin (OPN) is one of the proteins overexpressed in ovarian cancer and is involved in tumorigenesis and metastasis. Alternative splicing of OPN leads to 3 isoforms, OPNa, OPNb, and OPNc.

Apoptosis and apoptotic mimicry: the Leishmania connection.

Different death-styles have been described in unicellular organisms. In most cases they evolve with phenotypic features similar to apoptotic death of animal cells, such as phosphatidylserine (PS) exposure, oligonucleosomal DNA fragmentation, and loss of mitochondrial transmembrane potential, hinting that similar mechanisms operate in both situations. However, the biochemical pathways underlying death in unicellular organisms are still unclear.

Cooperation between apoptotic and viable metacyclics enhances the pathogenesis of Leishmaniasis.

Mimicking mammalian apoptotic cells by exposing phosphatidylserine (PS) is a strategy used by virus and parasitic protozoa to escape host protective inflammatory responses. With Leishmania amazonensis (La), apoptotic mimicry is a prerogative of the intramacrophagic amastigote form of the parasite and is modulated by the host. Now we show that differently from what happens with amastigotes, promastigotes exposing PS are non-viable, non-infective cells, undergoing apoptotic death.

Mimicry of apoptotic cells by exposing phosphatidylserine participates in the establishment of amastigotes of Leishmania (L) amazonensis in mammalian hosts.

Signaling through exposed phosphatidylserine (PS) is fundamental for the TGFbeta1-dependent, noninflammatory phagocytosis of apoptotic cells. This same mechanism operates in the internalization of amastigotes of Leishmania (L) amazonensis (L(L)a) in a process quoted as apoptotic mimicry. Now we show that the host modulates PS exposure by the amastigotes and, as a consequence, BALB/c mice-derived amastigotes expose significantly more PS than those derived from C57BL/6 mice.

Flow cytometric assessment of Leishmania spp metacyclic differentiation: validation by morphological features and specific markers.

Characterization of infective metacyclic promastigotes of Leishmania spp can be an essential step in several experimental protocols. Metacyclic forms of all Leishmania species display a typical morphology with short, narrow cell body, and an elongated flagellum. This feature suggests that metacyclics can be distinguished from procyclic forms by non-fluorimetric flow cytometric parameters thus enabling the follow-up of their appearance and acquisition of specific properties, during metacyclogenesis in in vitro cultures.