Involvement of the macrophage mannose-6-phosphate receptor in the recognition of Leishmania mexicana amazonensis

Saraiva, Elvira M.; Andrade, Arnaldo F.B.; Souza, Wanderley de

doi:10.1007/bf00538197

Cited by 17 publications

(13 citation statements)

References 29 publications

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“…There is some evidence in the literature that may help to explain these differences. First, it has been shown that different parasite surface molecules and macrophage receptors are involved in the initial cell-recognition process (Saraiva et al 1987;Russell et al 1992;Mosser and Rosenthal 1993). Second, it was observed that PVs containing infective promastigotes do not fuse efficiently with endosomes (Desjardins and Descouteaux 1997), whereas extensive fusion occurs with PVs containing amastigotes.…”

Section: Discussionmentioning

confidence: 97%

“…Microscopic studies have demonstrated differences in the early ultrastructural phagocytic events of both Leishmania forms by macrophages (Strauss et al 1993). The amastigote phagocytic rate by macrophages is greater (Alexander and Vickerman 1975;Saraiva et al 1987) and it was also observed that NAD(P)H activity was greater in PVs containing promastigotes (Pimenta and De Souza 1988). However, biochemical studies carried out in the isolated PV, which may help to clarify the mechanisms involved in its biogenesis, are almost absent.…”

Section: Introductionmentioning

confidence: 87%

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Biochemical analysis of proteins and lipids found in parasitophorous vacuoles containing Leishmania amazonensis

Henriques

Atella

Bonilha

et al. 2003

Parasitology Research

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One fundamental step of Leishmania-macrophage interaction is the phase of parasite internalization through an endocytic process, with the formation of the parasitophorous vacuole (PV). The present study analyzed this process using two approaches. First, to investigate the host cell proteins which take part in this compartment, the macrophage surface was biotinilated and allowed to interact with both Leishmania forms, the PV was then isolated, and the biotinilated proteins were analyzed by Western blot. The results obtained showed that the isolated PV from macrophages infected for 60 min with infective promastigotes displayed high molecular weight proteins, 220 kDa and 180 kDa, contrary to the isolated PV obtained from amastigotes. The isolated PV from amastigotes, after 60 min interaction, displayed a faint, biotinilated protein profile, in contrast to the PV containing amastigote which, after 30 min interaction, displayed a strong protein profile in the range of 120 kDa and 40-60 kDa. The biotinilated protein profile may represent proteins distributed in the PV membrane and may also correspond to biotinilated proteins incorporated by the intracellular parasite, as observed by confocal microscopy. In a second approach, to investigate the PV phospholipid composition, macrophages were incubated with (32)P, allowed to interact with the parasites, and the isolated PV was then processed for phospholipid analysis by thin layer chromatography and scintillation counting. An increase in the levels of lysophosphatidylcholine was observed in infected macrophages. The isolated PV from infective promastigotes and amastigotes, after 60 min interaction, displayed high levels of phosphatidylcholine. Then the PV was ruptured and the intravacuolar parasite's (32)P phospholipid composition was analyzed by TLC; and labeling of the parasites was found, suggesting that phospholipids from the macrophage are transferred to the parasite. Taken together, the results obtained show that several proteins and phospholipids found in the plasma membrane of the macrophage are also found in the PV compartment.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 87%

Biochemical analysis of proteins and lipids found in parasitophorous vacuoles containing Leishmania amazonensis

Henriques

Atella

Bonilha

et al. 2003

Parasitology Research

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“…Furthermore, binding of L. monocytogenes to McCoy cells was significantly inhibited by M6P in a dose-dependent manner. Competitive inhibition studies using soluble M6P as an inhibitor of binding of other ligands are established techniques for the investigation of IGFIIR function (37,62,73). The M6P effects were specific, because G6P, a closely related analogue that does not bind to the IGFIIR (38), had no effect.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Insulin-Like Growth Factor II Receptor as a Novel Receptor for Binding and Invasion by Listeria monocytogenes

et al. 2006

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The gram-positive bacterium Listeria monocytogenes causes a life-threatening disease known as listeriosis. The mechanism by which L. monocytogenes invades mammalian cells is not fully understood, but the processes involved may provide targets to prevent and treat listeriosis. Here, for the first time, we have identified the insulin-like growth factor II receptor (IGFIIR; also known as the cation-independent mannose 6-phosphate receptor CI M6PR or CD222) as a novel receptor for binding and invasion of Listeria species. Random peptide phage display was employed to select a peptide sequence by panning with immobilized L. monocytogenes cells; this peptide sequence corresponds to a sequence within the mannose 6-phosphate binding site of the IGFIIR. All Listeria spp. specifically bound the labeled peptide but not a control peptide, which was demonstrated using fluorescence spectrophotometry and fluorescence-activated cell sorting. Further evidence for binding of the receptor by L. monocytogenes and L. innocua was provided by affinity purification of the bovine IGFIIR from fetal calf serum by use of magnetic beads coated with cell preparations of Listeria spp. as affinity matrices. Adherence to and invasion of mammalian cells by L. monocytogenes was significantly inhibited by both the synthetic peptide and mannose 6-phosphate but not by appropriate controls. These observations indicate a role for the IGFIIR in the adherence and invasion of L. monocytogenes of mammalian cells, perhaps in combination with known mechanisms. Ligation of IGFIIR by L. monocytogenes may be a novel mechanism that contributes to the regulation of infectivity, possibly in combination with other mechanisms.The gram-positive bacterium Listeria monocytogenes is a human pathogen that causes listeriosis primarily in immunosuppressed individuals. Symptoms are flu-like, and yet disease may progress to severe complications such as meningitis, septicemia, spontaneous abortion, or listeriosis of the newborn (28,39,83). The number of cases of listeriosis range from 40 to 44 per year in Australia (3, 79) and average 100 per year in the United States (13). Although the incidence of listeriosis is low compared to that of other foodborne diseases, the associated mortality rate is high (approximately 30%) (39, 74, 83). Knowledge of the molecular mechanisms underlying the binding and internalization of Listeria spp. to host cells is limited. New antibiotic, vaccine, and diagnostic targets are needed to prevent and treat infection by Listeria spp., and understanding the processes of adherence and entry into cells is fundamental to defining appropriate preventative and therapeutic strategies.Random peptide phage display has been successfully employed to identify new receptors and receptor ligands (44,52,53,82) and in epitope mapping and mimicking of protein antigens and antibodies (16,42,61) and drug discovery (40,52,78). In this study we employed random peptide phage display in an attempt to identify novel surface antigens that may be used as therapeutic targets ...

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“…Promastigotes labeled with PKH26 showed a strong and uniform staining pattern (C, D); early interaction with macrophages for 15 min revealed partial staining of adherent promastigotes (arrows, G, H), and later the diusion of a probe through a macrophage was observed, with adherent (arrowheads) and intravacuolar (arrows) parasites being slightly stained, after 60 min of interaction (K, L). (v Parasitophorous vacuole) Bars 10 lm to a large extent (Saraiva et al 1987) via cup-shaped extensions, whereas ingestion of promastigotes takes place via long and prominent surface projections (Strauss et al 1993), which would explain the clearer labeling of the contact area in the case of promastigotes. Later the intravacuolar parasites were labeled, indicating transfer of the host's membrane lipophilic molecules.…”

Section: Discussionmentioning

confidence: 99%

“…Both promastigote and amastigote have to attach to the phagocyte surface before they are taken in (Mosser and Rosenthal 1993). Internalization occurs via a conventional phagocytic process mediated by macrophage receptors, and several surface receptor-ligand systems have been shown to participate in the recognition process (Chang 1983;Saraiva et al 1987;Puentes et al 1988;Soteriadou et al 1992). Depending on the Leishmania form involved, the protozoan surface composition may select dierent receptor sites (Saraiva et al 1987) on the phagocytic cell membrane, modifying the PV membrane composition, mainly during the initial phagocytic stages, where the PV is formed by part of the plasma membrane, to which the parasite has adhered.…”

Section: Introductionmentioning

confidence: 99%

Redistribution of plasma-membrane surface molecules during formation of the Leishmania amazonensis -containing parasitophorous vacuole

Henriques

Souza²

2000

Parasitology Research

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Leishmania amazonensis presents two developmental stages that gain access to the host macrophage through phagocytosis. The protozoan resides in a membrane-bound compartment, the parasitophorous vacuole (PV), which can fuse with the endocytic system. For evaluation of the parasite/host-cell interaction process and of PV biogenesis, the two parasite forms or host-cell membrane whose surface had previously been labeled with specific probes for lipids, proteins, and sialoglycoconjugates were allowed to interact for periods varying from 5 to 15 min for adhesion and from 30 to 60 min for PV formation. The fate of fluorescent probes was followed by confocal laser scanning microscopy. In host cells previously labeled with PKH26, DTAF and FITC-thiosemicarbazide, which label membrane lipids, proteins, and sialoglycoconjugates, respectively, interaction with both protozoan forms revealed that adhesion to the macrophage was sufficient for labeling of the parasite surface. In addition, recently formed PVs displayed strongly labeled intravacuolar parasites, except for amastigote-macrophage interaction in a DTAF-labeled macrophage that displayed slight labeling of intravacuolar parasites, with the membrane lining the PV evidently being stained. Therefore, the vacuole modulation presents some particularities such that different host-cell membrane components may be selected, depending on the protozoan form involved. Thereafter, amastigotes labeled with the probes mentioned above displayed a diffuse labeling pattern after interaction with unlabeled macrophages, suggesting the spreading of Leishmania surface molecules during the initial parasite-invasion stages. In particular, intravacuolar DTAF-labeled amastigotes showed a delineating halo around the PV, with the intravacuolar parasite being partially labeled. Promastigotes could not be labeled with 5-(4,6-dichlorotriazinyl)aminofluorescein (DTAF) or with fluorescein-5-thiosemicarbazide, but promastigotes labeled with PKH26 lost the fluorescent probe during the invasion process such that slightly labeled promastigotes were seen inside the PV. These observations indicate the existence of a dynamic process of exchange of membrane-associated glycoproteins and lipids between the parasite and the host cell.

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Involvement of the macrophage mannose-6-phosphate receptor in the recognition of Leishmania mexicana amazonensis

Cited by 17 publications

References 29 publications

Biochemical analysis of proteins and lipids found in parasitophorous vacuoles containing Leishmania amazonensis

Biochemical analysis of proteins and lipids found in parasitophorous vacuoles containing Leishmania amazonensis

Identification of the Insulin-Like Growth Factor II Receptor as a Novel Receptor for Binding and Invasion by Listeria monocytogenes

Redistribution of plasma-membrane surface molecules during formation of the Leishmania amazonensis -containing parasitophorous vacuole

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