ABSTRACT
Plasmodium vivax infects human erythrocytes through a major pathway that requires interaction between an apical parasite protein, the Duffy binding protein (PvDBP) and its receptor on reticulocytes, the Duffy antigen/receptor for chemokines (DARC). The importance of the interaction between PvDBP (region II, DBPII) and DARC to P. vivax infection has motivated our malaria research group at Oswaldo Cruz Foundation (state of Minas Gerais, Brazil) to conduct a number of immunoepidemiological studies to characterise the naturally acquired immunity to PvDBP in populations living in the Amazon rainforest. In this review, we provide an update on the immunology and molecular epidemiology of PvDBP in the Brazilian Amazon - an area of markedly unstable malaria transmission - and compare it with data from other parts of Latin America, as well as Asia and Oceania.
Subject(s)
Humans , Antigens, Protozoan/immunology , Malaria Vaccines/immunology , Malaria, Vivax/prevention & control , Plasmodium vivax/immunology , Protozoan Proteins/immunology , Receptors, Cell Surface/immunology , Antibodies, Protozoan/blood , Antigens, Protozoan/chemistry , Brazil , Enzyme-Linked Immunosorbent Assay , Geography, Medical , Protozoan Proteins/chemistry , Receptors, Cell Surface/chemistryABSTRACT
The spleen plays a crucial role in the development of immunity to malaria, but the role of pattern recognition receptors (PRRs) in splenic effector cells during malaria infection is poorly understood. In the present study, we analysed the expression of selected PRRs in splenic effector cells from BALB/c mice infected with the lethal and non-lethal Plasmodium yoelii strains 17XL and 17X, respectively, and the non-lethal Plasmodium chabaudi chabaudi AS strain. The results of these experiments showed fewer significant changes in the expression of PRRs in AS-infected mice than in 17X and 17XL-infected mice. Mannose receptor C type 2 (MRC2) expression increased with parasitemia, whereas Toll-like receptors and sialoadhesin (Sn) decreased in mice infected with P. chabaudi AS. In contrast, MRC type 1 (MRC1), MRC2 and EGF-like module containing mucin-like hormone receptor-like sequence 1 (F4/80) expression decreased with parasitemia in mice infected with 17X, whereas MRC1 an MRC2 increased and F4/80 decreased in mice infected with 17XL. Furthermore, macrophage receptor with collagenous structure and CD68 declined rapidly after initial parasitemia. SIGNR1 and Sn expression demonstrated minor variations in the spleens of mice infected with either strain. Notably, macrophage scavenger receptor (Msr1) and dendritic cell-associated C-type lectin 2 expression increased at both the transcript and protein levels in 17XL-infected mice with 50% parasitemia. Furthermore, the increased lethality of 17X infection in Msr1 -/- mice demonstrated a protective role for Msr1. Our results suggest a dual role for these receptors in parasite clearance and protection in 17X infection and lethality in 17XL infection.
Subject(s)
Animals , Female , Mice , Lectins, C-Type/immunology , Malaria/parasitology , Mannose-Binding Lectins/immunology , Plasmodium chabaudi/immunology , Plasmodium yoelii/immunology , Receptors, Cell Surface/immunology , Receptors, Scavenger/immunology , Spleen/parasitology , Toll-Like Receptors/immunology , Flow Cytometry , Lectins, C-Type/genetics , Mice, Inbred BALB C , Microarray Analysis , Malaria/immunology , Mannose-Binding Lectins/genetics , Parasitemia/immunology , Receptors, Cell Surface/genetics , Receptors, Scavenger/genetics , Spleen/immunology , Toll-Like Receptors/geneticsABSTRACT
Plasmodium vivax is the most prevalent malaria parasite on the American continent. It generates a global burden of 80-100 million cases annually and represents a tremendous public health problem, particularly in the American and Asian continents. A malaria vaccine would be considered the most cost-effective measure against this vector-borne disease and it would contribute to a reduction in malaria cases and to eventual eradication. Although significant progress has been achieved in the search for Plasmodium falciparum antigens that could be used in a vaccine, limited progress has been made in the search for P. vivax components that might be eligible for vaccine development. This is primarily due to the lack of in vitro cultures to serve as an antigen source and to inadequate funding. While the most advanced P. falciparum vaccine candidate is currently being tested in Phase III trials in Africa, the most advanced P. vivax candidates have only advanced to Phase I trials. Herein, we describe the overall strategy and progress in P. vivax vaccine research, from antigen discovery to preclinical and clinical development and we discuss the regional potential of Latin America to develop a comprehensive platform for vaccine development.
Subject(s)
Animals , Humans , Antigens, Protozoan/immunology , Malaria Vaccines/immunology , Malaria, Vivax , Plasmodium vivax/immunology , Clinical Trials as Topic , Latin America , Malaria, Vivax/immunology , Protozoan Proteins/immunology , Receptors, Cell Surface/immunologyABSTRACT
A polysaccharide-rich fraction (ATF) of medicinal mushroom Agaricus brasiliensis was evaluated on the candidacidal activity, H2O2 and nitric oxide (NO) production, and expression of mannose receptors by murine peritoneal macrophages. Mice received three intraperitoneal (i.p.) injections of ATF and after 48 h their peritoneal resident macrophages were assayed against Candida albicans yeast forms. The treatment increased fungicidal activity and it was associated with higher levels of H2O2, whereas NO production was not affected. We also found that the treatment enhances mannose receptor expression by peritoneal macrophages, which are involved in the attachment and phagocytosis of non-opsonized microorganisms. Treatment of animals with ATF was able to enhance the clearance of C. albicans during the first 6 h after the experimental i.p. infection. Our results suggest that this extract can increase host resistance against some infectious agents through the stimulation of microbicidal activity of macrophages.
Subject(s)
Animals , Male , Mice , Agaricus/chemistry , Candida albicans/immunology , Macrophages, Peritoneal/immunology , Polysaccharides/pharmacology , Candida albicans/drug effects , Hydrogen Peroxide/immunology , Lectins, C-Type/immunology , Mice, Inbred BALB C , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/microbiology , Mannose-Binding Lectins/immunology , Nitric Oxide/biosynthesis , Phagocytosis/drug effects , Polysaccharides/isolation & purification , Receptors, Cell Surface/immunologyABSTRACT
BACKGROUND & OBJECTIVE: The understanding of the pathogenesis of psoriasis vulgaris has focused on T cell mediated immune disorder for many years. Recent studies provide evidence that dendritic cells may be of major importance as regulatory cells driving the psoriasis tissue reaction, and they are one of the therapeutic targets. In order to further characterize the role of dendritic cells in psoriasis, this study was designed to assess the differentiation of dendritic cells from monocytes (MoDC), the expression of phagocytosis related receptors by MoDC, their endocytic activity for fluorescent beads and lucifer yellow as well as their superoxide generation in patients with psoriasis. METHODS: Twenty eight patients with psoriasis vulgaris and 12 healthy controls were included in the study. MoDC were obtained by culturing monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 5 days. Cell surface expression of CD1a, CD14, CD40, CD80, CD83, CD86, HLA-DR, mannose receptor (MR) and Fcg receptors by MoDC and their endocytosis of dextran and lucifer yellow were analyzed by flow cytometry. Zymosan ingestion was measured to access the phagocytosis of MoDC. RESULTS: Differentiation of monocytes to dendritic cells was upregulated in patients manifested as significantly increased expression of CD40, CD80, CD86 and HLA-DR compared with that in healthy controls (P<0.01). Expression of MR and Fcg receptor II (CD32) by MoDC was significantly increased in patients with psoriasis as well (P<0.01). Endocytosis of dextran but not lucifer yellow in patients was significantly higher than controls (P<0.01), and significantly enhanced phagocytosis by increasing zymosan ingestion was also observed (P<0.01) in patients. Taken together, endocytic and phagocytic activity of MoDC in psoriasis was increased than normal persons. INTERPRETATION & CONCLUSION: Enhanced activity of dendritic cells binding and capturing foreign antigens for subsequent antigen presentation and the initiation of immune responses in psoriasis may contribute to the pathogenesis of the disease. The upregulated expression of MR and the enhanced endocytic activity of DC might be an explanation for the absence of skin infection observed in psoriasis.
Subject(s)
Adolescent , Adult , Aged , Biomarkers/metabolism , Cell Differentiation/physiology , China , Dendritic Cells/cytology , Endocytosis/physiology , Female , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Lectins, C-Type/immunology , Male , Mannose-Binding Lectins/immunology , Middle Aged , Monocytes/cytology , Phagocytosis/physiology , Psoriasis/immunology , Random Allocation , Receptors, Cell Surface/immunology , Receptors, IgG/immunologyABSTRACT
Cell mediated immune responses play a prominent role in syphilis, which is caused by Treponema pallidum. The role of dendritic cells (DC) in the syphilitic infection is not well understood in human. In the present study, we studied interaction of T. pallidum with DC, generated from human peripheral blood mononuclear cells with GM-CSF and IL-4. After adding T. pallidum for 16 hours to immature DC at culture day 7, the change of surface antigens on DC was monitored by flow cytometry, the amount of IL-12 in culture supernatant of DC was measured by ELISA and T cell stimulatory capacity of DC was checked in mixed lymphocyte reaction (MLR). We have observed an efficient phagocytosis of T. pallidum by electron microscopy as early as 2 hours after addition of T. pallidum to DC. Interaction of DC with T. pallidum resulted in increased surface expression of CD83 which was proportionally increased according to the number of T. pallidum. Expressions of CD80, CD86 and HLA-DR on DC were slightly increased. The amount of IL-12 in the culture supernatant of DC was increased (1, 099pg/ml) after the addition of T. pallidum. T. pallidum-infected DC also displayed enhanced T cell stimulatory capacity in MLR. As seen from the above, we observed phagocytosis of T. pallidum by DC as early as 2 hours after addition of T. pallidum to DC and found that T. pallidum can stimulate DC maturation which mean that DC modulate an protective immune response during T. pallidum infection.
Subject(s)
Humans , Cells, Cultured , Dendritic Cells/cytology , Interleukin-12/metabolism , Lymphocyte Culture Test, Mixed , Microscopy, Electron , Phagocytosis/immunology , Receptors, Cell Surface/immunology , Syphilis/immunology , T-Lymphocytes/immunology , Treponema pallidum/immunologyABSTRACT
The mammalian oocyte is surrounded by an extra-cellular matrix, the zona pellucida (ZP), composed of three major glycoproteins (ZP1, ZP2 and ZP3). The ZP glycoproteins, by virtue of their tissue specificity and critical role during mammalian fertilization, have emerged as potential candidate antigens for the development of an immunocontraceptive vaccine. Molecular characterization of ZP glycoproteins from several species, reveals a variable degree of homology among the deduced primary amino acid sequences, which provided an opportunity to undertake active immunization studies in heterologous animal models. Active immunization of various animal species with either native ZP glycoproteins or those obtained by recombinant DNA technology led to the inhibition of fertility. Thus ZP glycoproteins based immunocontraceptive vaccines offer an attractive proposition for controlling wild life population. To make it a practical proposition, additional research inputs are required to optimize and devise novel strategies for vaccine delivery. Observed ovarian dysfunction, often associated with immunization by ZP glycoproteins is one of the major stumbling blocks for their use in humans. Ongoing studies to delineate appropriate B cell epitopes of ZP glycoproteins that are devoid of oophoritogenic T-cell epitopes, which will inhibit fertility without concomitant oophoritis, will be critical to determine their feasibility for human use.
Subject(s)
Animals , Contraception, Immunologic/methods , Egg Proteins/immunology , Humans , Membrane Glycoproteins/immunology , Receptors, Cell Surface/immunology , Vaccines, Contraceptive , Zona Pellucida/chemistrySubject(s)
Humans , Animals , Mice , Rabbits , Graft Rejection/immunology , Histocompatibility Antigens/immunology , Genes, MHC Class I/immunology , Immunotherapy , Cell Adhesion Molecules/immunology , Receptors, Cell Surface/immunology , Receptors, Interleukin-2/immunology , Graft Rejection/therapyABSTRACT
Se exponen los criterios actuales acerca de la estructura del receptor de las células T y de las características de las cadenas *, ß y *. Se analiza la composición de los genes que codifican estos polipéptidos, los que se comportan en forma semejante a los genes de la inmunoglobulina. Se comenta el estudio del reordenamiento y expresión de los genes del receptor T durante el desarrollo fetal y la diferenciación intratímica de las células T. Se plantea la utilidad de la aplicación clínica del estudio del reordenamiento de los genes del receptor de las células T en la caraterización y diagnóstico diferencial de los síndromes linfoproliferativos. Se señala que la reciente identificación de un presunto nuevo receptor de las células T y del polipéptido que se denomina cadena delta seguramente contribuirá a una ampliación de los conocimientos sobre este tema