scholarly journals Role of SLC11A1 gene in disease resistance

2012 ◽  
Vol 28 (1) ◽  
pp. 99-106 ◽  
Author(s):  
N. Thomas ◽  
S. Joseph
Keyword(s):  
Disease Resistance ◽  
Genetic Resistance ◽  
Integral Membrane Protein ◽  
Natural Resistance ◽  
Human Beings ◽  
Economic Traits ◽  
Slc11a1 Gene ◽  
Breeding Programmes ◽  
Macrophage Protein

Genetic improvement in livestock was achieved earlier by selective breeding of individuals with superior phenotypes. Now due to the advances in molecular genetics and biotechnology candidate genes of economic traits can be included in selection for breeding programmes. Genes responsible for the resistance/susceptibility to infections with various pathogens (Major Histo Compatibility (MHC) genes, Solute Carrier family11 member A1 (SLC11A1) gene, Toll Like Receptor (TLR) genes etc.), have been recently identified and characterized in human beings as well as in many animals. Among these the role of SLC11A1 gene is very important due to its association with resistance/ susceptibility to various intracellular pathogens in human as well as in livestock species. The SLC11A1 gene, formerly known as natural resistance-associated macrophage protein 1 (NRAMP1) encodes an integral membrane protein regulating the activity of macrophages. Genetic resistance/ susceptibility to diseases due to candidate gene polymorphisms could be used in selection and breeding for disease resistance in animals.

scholarly journals Genetically resistant sheep avoid parasites to a greater extent than do susceptible sheep

2007 ◽  
Vol 274 (1620) ◽  
pp. 1839-1844 ◽  
Author(s):  
M.R Hutchings ◽  
K.J Knowler ◽  
R McAnulty ◽  
J.C McEwan
Keyword(s):  
Immune Function ◽  
Genetic Resistance ◽  
Livestock Breeding ◽  
Breeding Programmes ◽  
Grazing Systems ◽  
Forage Intake ◽  
Host Behaviour ◽  
Selection Of ◽  
Parasite Avoidance

Livestock breeding programmes have created resistant (R) and susceptible (S) sheep that differ in their ability to control parasites through their immune function but potentially also their grazing behaviour (i.e. parasite avoidance). Using the Perendale genetic lines, we tested the hypothesis that R-sheep avoid parasites more effectively, reducing their parasite exposure/challenge, compared with S-sheep. However, in grazing systems, parasite-rich areas are also forage rich, suggesting that parasite avoidance behaviours are associated with nutritional penalties. We first created a naturally heterogeneous sward structure of gaps and tussocks and then used focal behavioural observations to quantify the sward selection of R- and S-sheep. Tussock swards were more nitrogen rich (41%), offered increased forage intake rates (32%) and contained 17 times more parasite larvae than gap swards. All the animals avoided grazing the tussock swards. However, the R-sheep grazed the tussock swards to a lesser degree than the S-sheep. We conclude that selection for genetic resistance has resulted in animals that, despite being well armed to fight parasitism through improved immune function, adopt parasite avoidance strategies with associated nutritional disadvantages. This experiment highlights the role of host behaviour in the control of parasitism and suggests that animals can be bred to avoid disease.

scholarly journals Host Resistance to Intracellular Infection: Mutation of Natural Resistance-associated Macrophage Protein 1 (Nramp1) Impairs Phagosomal Acidification

1998 ◽  
Vol 188 (2) ◽  
pp. 351-364 ◽  
Author(s):  
David J. Hackam ◽  
Ori D. Rotstein ◽  
Wei-jian Zhang ◽  
Samantha Gruenheid ◽  
Philippe Gros ◽  
...  
Keyword(s):  
Integral Membrane Protein ◽  
Natural Resistance ◽  
Wild Type ◽  
Intracellular Parasites ◽  
Late Endosomes ◽  
Latex Beads ◽  
Buffering Power ◽  
Ratio Imaging ◽  
Macrophage Protein ◽  
Phagosomal Membrane

The mechanisms underlying the survival of intracellular parasites such as mycobacteria in host macrophages remain poorly understood. In mice, mutations at the Nramp1 gene (for natural resistance-associated macrophage protein), cause susceptibility to mycobacterial infections. Nramp1 encodes an integral membrane protein that is recruited to the phagosome membrane in infected macrophages. In this study, we used microfluorescence ratio imaging of macrophages from wild-type and Nramp1 mutant mice to analyze the effect of loss of Nramp1 function on the properties of phagosomes containing inert particles or live mycobacteria. The pH of phagosomes containing live Mycobacterium bovis was significantly more acidic in Nramp1- expressing macrophages than in mutant cells (pH 5.5 ± 0.06 versus pH 6.6 ± 0.05, respectively; P <0.005). The enhanced acidification could not be accounted for by differences in proton consumption during dismutation of superoxide, phagosomal buffering power, counterion conductance, or in the rate of proton “leak”, as these were found to be comparable in wild-type and Nramp1-deficient macrophages. Rather, after ingestion of live mycobacteria, Nramp1-expressing cells exhibited increased concanamycin-sensitive H+ pumping across the phagosomal membrane. This was associated with an enhanced ability of phagosomes to fuse with vacuolar-type ATPase–containing late endosomes and/or lysosomes. This effect was restricted to live M. bovis and was not seen in phagosomes containing dead M. bovis or latex beads. These data support the notion that Nramp1 affects intracellular mycobacterial replication by modulating phagosomal pH, suggesting that Nramp1 plays a central role in this process.

scholarly journals Two NRAMP6 Isoforms Function as Iron and Manganese Transporters and Contribute to Disease Resistance in Rice

2017 ◽  
Vol 30 (5) ◽  
pp. 385-398 ◽  
Author(s):  
Cristina Peris-Peris ◽  
Albert Serra-Cardona ◽  
Ferrán Sánchez-Sanuy ◽  
Sonia Campo ◽  
Joaquin Ariño ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Crop Protection ◽  
Underlying Disease ◽  
Essential Elements ◽  
Natural Resistance ◽  
Loss Of Function ◽  
Metal Transporters ◽  
Enhanced Resistance ◽  
Iron And Manganese

Metal ions are essential elements for all living organisms. However, metals can be toxic when present in excess. In plants, metal homeostasis is partly achieved through the function of metal transporters, including the diverse natural resistance-associated macrophage proteins (NRAMP). Among them, the OsNramp6 gene encodes a previously uncharacterized member of the rice NRAMP family that undergoes alternative splicing to produce different NRAMP6 proteins. In this work, we determined the metal transport activity and biological role of the full-length and the shortest NRAMP6 proteins (l-NRAMP6 and s-NRAMP6, respectively). Both l-NRAMP6 and s-NRAMP6 are plasma membrane-localized proteins that function as iron and manganese transporters. The expression of l-Nramp6 and s-Nramp6 is regulated during infection with the fungal pathogen Magnaporthe oryzae, albeit with different kinetics. Rice plants grown under high iron supply show stronger induction of rice defense genes and enhanced resistance to M. oryzae infection. Also, loss of function of OsNramp6 results in enhanced resistance to M. oryzae, supporting the idea that OsNramp6 negatively regulates rice immunity. Furthermore, nramp6 plants showed reduced biomass, pointing to a role of OsNramp6 in plant growth. A better understanding of OsNramp6-mediated mechanisms underlying disease resistance in rice will help in developing appropriate strategies for crop protection.

scholarly journals Natural Resistance to Intracellular Infections

2000 ◽  
Vol 192 (9) ◽  
pp. 1237-1248 ◽  
Author(s):  
Nada Jabado ◽  
Andrzej Jankowski ◽  
Samuel Dougaparsad ◽  
Virginie Picard ◽  
Sergio Grinstein ◽  
...  
Keyword(s):  
Divalent Cations ◽  
Fluorescence Emission ◽  
Integral Membrane Protein ◽  
Peritoneal Macrophages ◽  
Natural Resistance ◽  
Susceptibility To Infection ◽  
The Difference ◽  
Macrophage Protein ◽  
Phagosomal Membrane ◽  
Intracellular Infections

Mutations at the natural resistance–associated macrophage protein 1 (Nramp1) locus cause susceptibility to infection with antigenically unrelated intracellular pathogens. Nramp1 codes for an integral membrane protein expressed in the lysosomal compartment of macrophages, and is recruited to the membrane of phagosomes soon after the completion of phagocytosis. To define whether Nramp1 functions as a transporter at the phagosomal membrane, a divalent cation-sensitive fluorescent probe was designed and covalently attached to a porous particle. The resulting conjugate, zymosan–FF6, was ingested by macrophages and its fluorescence emission was recorded in situ after phagocytosis, using digital imaging. Quenching of the probe by Mn2+ was used to monitor the flux of divalent cations across the phagosomal membrane in peritoneal macrophages obtained from Nramp1-expressing (+/+) and Nramp1-deficient (−/−) macrophages. Phagosomes from Nramp1+/+ mice extrude Mn2+ faster than their Nramp−/− counterparts. The difference in the rate of transport is eliminated when acidification of the phagosomal lumen is dissipated, suggesting that divalent metal transport through Nramp1 is H+ dependent. These studies suggest that Nramp1 contributes to defense against infection by extrusion of divalent cations from the phagosomal space. Such cations are likely essential for microbial function and their removal from the phagosomal microenvironment impairs pathogenesis, resulting in enhanced bacteriostasis or bactericidal activity.

scholarly journals Role of Nramp1 Deletion inChlamydia Infection in Mice

2000 ◽  
Vol 68 (8) ◽  
pp. 4831-4833 ◽  
Author(s):  
Sukumar Pal ◽  
Ellena M. Peterson ◽  
Luis M. de la Maza
Keyword(s):  
Chlamydia Trachomatis ◽  
Chlamydial Infection ◽  
Chlamydia Pneumoniae ◽  
Natural Resistance ◽  
Wild Type ◽  
Intranasal Infection ◽  
Macrophage Protein

ABSTRACT Elicited macrophages from 129sv mice with a functional deletion of the natural-resistance-associated macrophage protein 1 gene (Nramp1) were shown to be as susceptible as wild-type mice to infection with the Chlamydia trachomatis mouse pneumonitis and L3 serovars and to Chlamydia pneumoniae. Furthermore, the two groups of mice were shown to be similarly susceptible to an intranasal infection with these microorganisms. In conclusion, the Nramp1 gene does not appear to play a major role in the regulation of the susceptibility of mice to a chlamydial infection.

scholarly journals Human genes in TB infection: their role in immune response

2016 ◽  
Vol 69 (1) ◽  
Author(s):  
D. Lykouras ◽  
F. Sampsonas ◽  
A. Kaparianos ◽  
K. Karkoulias ◽  
G. Tsoukalas ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune ◽  
Natural Resistance ◽  
Cell Mediated Immunity ◽  
Th1 Cell ◽  
Human Genes ◽  
Solute Carrier ◽  
Macrophage Protein ◽  
Ongoing Concern

Tuberculosis (TB) caused by the human pathogen Mycobacterium tuberculosis, is the leading cause of morbidity and mortality caused by infectious agents worldwide. Recently, there has been an ongoing concern about the clarification of the role of specific human genes and their polymorphisms involved in TB infection. In the vast majority of individuals, innate immune pathways and Thelper 1 (Th1) cell mediated immunity are activated resulting in the lysis of the bacterium. Firstly, PTPN22 R620W polymorphism is involved in the response to cases of infection. The Arg753Gln polymorphism in TLR-2 leads to a weaker response against the M. tuberculosis. The gene of the vitamin D receptor (VDR) has a few polymorphisms (BsmI, ApaI, Taq1, FokI) whose mixed genotypes alter the immune response. Solute carrier family 11 member (SLC11A1) is a proton/divalent cation antiporter that is more familiar by its former name NRAMP1 (natural resistance associated macrophage protein 1) and can affect M. tuberculosis growth. Polymorphisms of cytokines such as IL-10, IL-6, IFN-g, TNF-a, TGF-b1 can affect the immune response in various ways. Finally, a major role is played by M. tuberculosis antigens and the Ras-associated small GTP-ase 33A. As far as we know this is the first review that collates all these polymorphisms in order to give a comprehensive image of the field, which is currently evolving.

Genetic analysis of SLC11A1 polymorphisms in multiple sclerosis patients

2004 ◽  
Vol 10 (6) ◽  
pp. 618-620 ◽  
Author(s):  
Manuel Comabella ◽  
Laura Altet ◽  
Francesc Peris ◽  
Pablo Villoslada ◽  
Armand Sánchez ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Natural Resistance ◽  
Bivalent Cation ◽  
Slc11a1 Gene ◽  
Late Endosomes ◽  
Solute Carrier ◽  
Macrophage Protein ◽  
Multiple Sclerosis Patients ◽  
Control Study

Solute carrier 11a1 (SLC11A1; formerly NRAMP1, where NRAMP stands for natural resistance-associated macrophage protein) is a proton/bivalent cation antiporter that localizes to late endosomes/lysosomes. SLC11A1 regulates macrophage functions that are of potential importance in the induction and/or maintenance of autoimmune diseases such as rheumatoid arthritis, type 1 diabetes and Crohn’s disease. We investigated SLC11A1 gene as a candidate gene for genetic susceptibility to multiple sclerosis (MS) in our population. Four SLC11A1 gene polymorphisms (5?GT repeat, D543N, 1729 -55del4 and 1729 -271del4) were analysed in a case-control study of 195 patients with MS and 125 control subjects. We found no evidence of association between SLC11A1 polymorphisms and MS susceptibility in the Spanish population.

Polymorphism of Nramp1 Gene and Its Association with Diarrhea in Pigs

2020 ◽  
Author(s):  
Lang Chen ◽  
Shuai Peng ◽  
Bao-Qiang Fu ◽  
Qian Du ◽  
Li Zhang ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Resistance Breeding ◽  
Natural Resistance ◽  
Large White ◽  
Chi Square ◽  
Exon 2 ◽  
Pig Breeds ◽  
Chi Square Test ◽  
Nramp1 Gene ◽  
Macrophage Protein

Background: Natural resistance associated macrophage protein 1 (Nramp1) is a relatively conservative gene that plays a crucial role in swine immune response and disease resistance. Methods: We identified the polymorphisms and gene variations in the exon 2 of Nramp1 using polymerase chain reaction–restriction fragment length polymorphism and investigated the correlation between the polymorphisms and piglet diarrhea in four pig breeds (Bamei, Duroc, Landrace, and Large White pigs). Result: The results showed that two alleles (A and B) were identified in all the pig breeds, three genotypes (AA, BB, and AB) were detected in Bamei and Large White breeds, and two genotypes (AA and AB) were detected in Landrace and Duroc breeds. Allele A and genotype AB were dominant in Bamei, Large White, and Landrace breeds, whereas genotype AA was dominant in Duroc pigs. A moderate polymorphism was observed in Landrace and Large White pigs, and polymorphism was abundant in Bamei pigs and low in Duroc pigs. The Chi-square test for Hardy–Weinberg equilibrium disclosed that the exon 2 of Nramp1 in the four breeds of pigs did not deviate from the Hardy–Weinberg balance (P less than 0.05). The results of association analysis showed a significant correlation between breed and piglet diarrhea (P less than 0.05), and the diarrhea score of Bamei pigs was much lower than those of the other breeds. The study could supply theoretical references for further functional research on Nramp1 gene and for screening genes related to disease-resistance breeding.

scholarly journals The Iron Transport Protein NRAMP2 Is an Integral Membrane Glycoprotein That Colocalizes with Transferrin in Recycling Endosomes

1999 ◽  
Vol 189 (5) ◽  
pp. 831-841 ◽  
Author(s):  
Samantha Gruenheid ◽  
François Canonne-Hergaux ◽  
Susan Gauthier ◽  
David J. Hackam ◽  
Sergio Grinstein ◽  
...  
Keyword(s):  
Cell Types ◽  
Integral Membrane Protein ◽  
Tissue Expression ◽  
Natural Resistance ◽  
Macrophage Cell ◽  
Recycling Endosomes ◽  
Endosomal Membrane ◽  
Lower Extent ◽  
Macrophage Protein ◽  
Insight Into

The natural resistance associated macrophage protein (Nramp) gene family is composed of two members in mammals, Nramp1 and Nramp2. Nramp1 is expressed primarily in macrophages and mutations at this locus cause susceptibility to infectious diseases. Nramp2 has a much broader range of tissue expression and mutations at Nramp2 result in iron deficiency, indicating a role for Nramp2 in iron metabolism. To get further insight into the function and mechanism of action of Nramp proteins, we have generated isoform specific anti-Nramp1 and anti-Nramp2 antisera. Immunoblotting experiments indicate that Nramp2 is present in a number of cell types, including hemopoietic precursors, and is coexpressed with Nramp1 in primary macrophages and macrophage cell lines. Nramp2 is expressed as a 90–100-kD integral membrane protein extensively modified by glycosylation (>40% of molecular mass). Subcellular localization studies by immunofluorescence and confocal microscopy indicate distinct and nonoverlapping localization for Nramp1 and Nramp2. Nramp1 is expressed in the lysosomal compartment, whereas Nramp2 is not detectable in the lysosomes but is expressed primarily in recycling endosomes and also, to a lower extent, at the plasma membrane, colocalizing with transferrin. These findings suggest that Nramp2 plays a key role in the metabolism of transferrin-bound iron by transporting free Fe2+ across the endosomal membrane and into the cytoplasm.

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