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1.
Biomarkers ; 17(1): 1-8, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22066602

ABSTRACT

CONTEXT: Identification of clinically relevant biomarkers is required for better diagnosis, prevention and treatment of tuberculosis. OBJECTIVE: In this review, potential host biomarkers in blood or blood cells in tuberculosis were identified by a systematic approach. METHODS: A total of 55 articles were selected from PubMed and Google Scholar that analyzed gene and or protein expression in humans in active and or latent TB. Articles were scored according to certain criteria and categorized as strong or weak studies. Biomarkers reported by more than one article or by a single strong article were identified as potential biomarkers. RESULTS: Six most promising markers (IP-10, IL-6, IL-10, IL-4, FOXP3 and IL-12) were identified based on their presence in both mycobacterial antigen-stimulated and -unstimulated samples. CONCLUSIONS: With this review we hope to provide a reliable guideline for biomarker studies in tuberculosis.


Subject(s)
Cytokines/blood , Latent Tuberculosis/blood , Latent Tuberculosis/diagnosis , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/diagnosis , Biomarkers/blood , Chemokine CXCL10/blood , Forkhead Transcription Factors/blood , Gene Expression Profiling , Humans , Information Storage and Retrieval , Interleukin-10/blood , Interleukin-12/blood , Interleukin-4/blood , Interleukin-6/blood , Latent Tuberculosis/immunology , Leukocytes, Mononuclear/immunology , Proteomics , Tuberculosis, Pulmonary/immunology
2.
J Insect Physiol ; 57(2): 231-45, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21078327

ABSTRACT

Gene silencing through RNA interference (RNAi) has revolutionized the study of gene function, particularly in non-model insects. However, in Lepidoptera (moths and butterflies) RNAi has many times proven to be difficult to achieve. Most of the negative results have been anecdotal and the positive experiments have not been collected in such a way that they are possible to analyze. In this review, we have collected detailed data from more than 150 experiments including all to date published and many unpublished experiments. Despite a large variation in the data, trends that are found are that RNAi is particularly successful in the family Saturniidae and in genes involved in immunity. On the contrary, gene expression in epidermal tissues seems to be most difficult to silence. In addition, gene silencing by feeding dsRNA requires high concentrations for success. Possible causes for the variability of success in RNAi experiments in Lepidoptera are discussed. The review also points to a need to further investigate the mechanism of RNAi in lepidopteran insects and its possible connection to the innate immune response. Our general understanding of RNAi in Lepidoptera will be further aided in the future as our public database at http://insectacentral.org/RNAi will continue to gather information on RNAi experiments.


Subject(s)
Gene Expression Regulation , Lepidoptera/genetics , Lepidoptera/immunology , RNA Interference , Animals , Databases, Genetic , Epidermis/growth & development , Gene Silencing , Immunity, Innate , Insect Proteins/drug effects , Insect Proteins/genetics , Insect Proteins/immunology , Lepidoptera/drug effects , Lepidoptera/growth & development , RNA, Double-Stranded/drug effects , Research Design
3.
J Immunol ; 179(10): 6943-51, 2007 Nov 15.
Article in English | MEDLINE | ID: mdl-17982085

ABSTRACT

Insect immune system comprises of both humoral and cellular defenses. Nodulation is one of the major, yet very poorly understood cellular responses against microbial infections in insects. Through screening for novel immune genes from an Indian saturniid silkmoth Antheraea mylitta, we identified a protein up-regulated in hemolymph within minutes upon bacterial challenge. We have shown here, for first time, the involvement of this novel protein in mediating nodulation response against bacteria and hence designated it as Noduler. Noduler possessed a characteristic reeler domain found in several extracellular matrix vertebrate proteins. Noduler was shown in vitro to bind a wide range of bacteria, yeast, and also insect hemocytes. Furthermore, Noduler specifically bound LPS, lipotechoic acid, and beta-1, 3 glucan components of microbial cell walls. RNA-interference mediated knock-down of the Noduler resulted in significant reduction in the number of nodules and consequent increase in bacterial load in larval hemolymph. The results suggest that the Noduler is widely conserved and is involved in very early clearance of bacteria by forming nodules of hemocytes and bacterial complexes in insects. The results would promote further studies for understanding of the crucial but hitherto overlooked nodulation mechanism in insects and also provide cues for the study of similar mammalian proteins whose function is not understood.


Subject(s)
Bombyx/immunology , Insect Proteins/immunology , Amino Acid Sequence , Animals , Bacterial Infections/genetics , Bacterial Infections/immunology , Bombyx/genetics , Cell Wall/immunology , Hemocytes/immunology , Hemolymph/immunology , Insect Proteins/genetics , Lipopolysaccharides/immunology , Mammals/genetics , Mammals/immunology , Molecular Sequence Data , Protein Structure, Tertiary/genetics , Sequence Homology, Amino Acid , Teichoic Acids/immunology , Up-Regulation/immunology
4.
Insect Biochem Mol Biol ; 37(7): 655-66, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17550822

ABSTRACT

Study on immune proteins in domesticated and wild silkmoths Bombyx mori and Antheraea mylitta, respectively, led to identification of a new class of antimicrobial proteins. We designated them as lysozyme-like proteins (LLPs) owing to their partial similarity with lysozymes. However, lack of characteristic catalytic amino acid residues essential for muramidase activity in LLPs puts them functionally apart from classical lysozymes. Two LLPs, one from B. mori (BLLP1) and the other from A. mylitta (ALLP1) expressed in a recombinant system, exhibited a broad-spectrum antibacterial action. Further investigation of the antibacterial mechanism revealed that BLLP1 is bacteriostatic rather than bactericidal against Escherichia coli and Micrococcus luteus. Substantial increase in hemolymph bacterial load was observed in B. mori upon RNA interference mediated in vivo knockdown of BLLP1. We demonstrate that the antibacterial mechanism of this protein depends on peptidoglycan binding unlike peptidoglycan hydrolysis or membrane permeabilization as observed with lysozymes and most other antimicrobial peptides. To our knowledge, this is the first report on functional analysis of novel, non-catalytic lysozyme-like family of antibacterial proteins that are quite apart functionally from classical lysozymes. The present analysis holds promise for functional annotation of similar proteins from other organisms.


Subject(s)
Anti-Bacterial Agents/chemistry , Bombyx/chemistry , Bombyx/immunology , Insect Proteins/chemistry , Animals , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Bombyx/genetics , Catalytic Domain , Cloning, Molecular , Escherichia coli/drug effects , Hemolymph/chemistry , Insect Proteins/immunology , Insect Proteins/isolation & purification , Insect Proteins/pharmacology , Microbial Sensitivity Tests , Micrococcus luteus/drug effects , Muramidase/chemistry , Muramidase/immunology , Muramidase/isolation & purification , Muramidase/metabolism , Peptidoglycan/metabolism , Protein Binding , Recombinant Proteins/chemistry , Recombinant Proteins/immunology , Recombinant Proteins/isolation & purification , Recombinant Proteins/pharmacology , Sequence Alignment , Sequence Homology, Amino Acid , Up-Regulation
5.
BMC Genomics ; 7: 184, 2006 Jul 21.
Article in English | MEDLINE | ID: mdl-16857061

ABSTRACT

BACKGROUND: In the recent years a strong resemblance has been observed between the insect immune system and the mammalian innate immune mechanisms suggesting their common origin. Among the insects, only the dipterans (Drosophila and various mosquito species) have been widely investigated for their immune responses towards diverse pathogens. In the present study we constructed and analysed the immune transcriptome of the lepidopteran Antheraea mylitta, an economically important Indian tasar silkmoth with a view to unravel the potential immune-related genes and pathways. RESULTS: An expressed sequence tag (EST) library was constructed from mRNA obtained from fat bodies of A. mylitta larvae that had been challenged by infection with Escherichia coli cells. We identified 719 unique ESTs from a total of 1412 sequences so generated. A third of the transcriptome showed similarity with previously characterized immune-related genes that included both the known and putative immune genes. Of the four putative novel defence proteins (DFPs) annotated by PSI-BLAST three showed similarity to extracellular matrix proteins from vertebrates implicated in innate immunity, while the fourth was similar to, yet distinct from, the anti-microbial protein cecropin. Finally, we analysed the expression profiles of 15 potential immune-related genes, and the majority of them were induced more prominently with E. coli compared to Micrococcus luteus. We also identified several unknown proteins, some of which could have probable immune-related functions based on the results of the ProDom analysis. CONCLUSION: The present study has identified many potential immune-related genes in A. mylitta some of which are vertebrate homologues and others are hitherto unreported putative defence proteins. Several genes were present as members of gene families, as has also been observed in other insect species.


Subject(s)
Gene Expression Profiling/methods , Moths/genetics , Moths/immunology , Amino Acid Sequence , Animals , Databases, Genetic , Escherichia coli , Expressed Sequence Tags , Histocompatibility Antigens Class II/classification , Histocompatibility Antigens Class II/genetics , Immunity, Innate/genetics , Larva/genetics , Larva/immunology , Larva/metabolism , Micrococcus luteus/pathogenicity , Molecular Sequence Data , Moths/microbiology , Protein Sorting Signals/genetics , Protein Structure, Tertiary , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid
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