Natural resistance to Salmonella infection, delayed hypersensitivity and Ir genes in different strains of mice

Plant, Janet E.; Glynn, A. A.

doi:10.1038/248345a0

Cited by 136 publications

(74 citation statements)

References 8 publications

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“…Two paralogous genes have been identified in human and mouse (Vidal et al, 1993;Barton et al, 1994;Gruenheid et al, 1995), although in mouse a third gene fragment, more closely related to mouse Nramp1 has been described, but not functionally characterised (Dosik et al, 1994). Nramp1, isolated for its role in controlling the growth of intracellular pathogens (Plant and Glynn, 1974;Bradley, 1974;Gros et al, 1981), is exclusively expressed in murine macrophages. The ubiquitously expressed Nramp2/Slc11a2 gene is implicated in the proton-dependent divalent cation uptake into red blood cells, the uptake of cations by the duodenal enterocyte, and in the transferrin-transferrin-receptor-mediated pathway of cellular iron assimilation (Fleming et al, 1997;Gunshin et al, 1997).…”

Section: Nramp1/slc11a1mentioning

confidence: 99%

Immunolocalisation of theD. melanogaster NramphomologueMalvolioto gut and Malpighian tubules provides evidence thatMalvolioandNramp2are orthologous

Folwell

Barton

Shepherd

2006

Journal of Experimental Biology

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SUMMARY Nramp (Slc11a1) genes in mammals are associated with the transport of iron and other divalent cations; Nramp1 in macrophages involved in the innate immune response against intracellular pathogens, and Nramp2 with duodenal iron uptake and the transferrin–transferrin-receptor pathway of iron assimilation. The Drosophila melanogaster Nramp-related gene is known as Malvolio. The localisation of Malvolio protein was inferred from the enhancer trap line initially used to isolate Malvolio in a screen for mutants with defects in taste perception. Here we describe the generation of a Malvolio-reactive polyclonal antibody and apply it to evaluate Malvolio localisation during stages of D. melanogaster development,and compare the results with the localisation of the enhancer trap line identified with beta-galactosidase. All immunolocalisation studies have been confirmed to be specific with Malvolio-blocking peptides. Our results demonstrated expression within Malpighian tubules, testis, brain, the amnioserosa of embryos, the larval and adult alimentary canal. Expression within the gut was of significant interest, as mammalian Nramp2 in the gut plays a primary role in the acquisition of dietary iron. We confirm expression within the central nervous system and in cells of the haematopoietic system. By immunohistochemistry we showed that expression within cells was either punctuate, diffuse cytoplasmic or plasma membrane associated, or both. The staining within the gut indicates a degree of conservation of components for iron acquisition between flies and mammals, suggesting that a comparable mechanism has been retained during evolution.

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Section: Nramp1/slc11a1mentioning

confidence: 99%

Immunolocalisation of theD. melanogaster NramphomologueMalvolioto gut and Malpighian tubules provides evidence thatMalvolioandNramp2are orthologous

Folwell

Barton

Shepherd

2006

Journal of Experimental Biology

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“…The first gene Ity was mapped to chromosome 1 and many strains of mice, such as BALB/c and C57BL/6, have the susceptible allele [24] which regulates the ability of host macrophages to kill Salmonella and other intracellular pathogens [19] or controls the rate of growth of Salmonella rather than the rate of killing [4]. Recently Vidal et al [27] identified Nramp1 as the gene underlying the Ity mutation.…”

Section: Introductionmentioning

confidence: 99%

Reliable ELISAs showing differences between resistant and susceptible lines in hens orally inoculated with Salmonella Enteritidis

Proux¹,

Jouy²,

Houdayer³

et al. 2002

Vet. Res.

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-Reliable ELISAs were investigated with the aim to select hen lines resistant to Salmonella Enteritidis and producing high levels of antibodies. In the first experiment, the relation between the humoral response and the bacteriological results was assessed on hens from the Y11 resistant line and the L2 susceptible line, orally inoculated with 10 8 CFU S. Enteritidis per animal. Antilipopolysaccharide (LPS) IgG titres were higher but the liver and spleen were less contaminated in hens from the Y11 line than in hens from the L2 line (p = 0.013, 0.031 and 0.026 respectively). In the second experiment, the hens were inoculated orally with 1.7 × 10 8 CFU S. Enteritidis per animal in order to select the ELISA methods showing the more significant differences. ELISAs were based on LPS, flagella, LPS from rough (LPS-R) and smooth strains (LPS-S) and detected IgG and IgM antibodies from sera and yolks. No between-line host response variation was observed in the yolk, with LPS-S and R antigens nor with anti-LPS IgM in the sera. Otherwise, significant differences were encountered between hen lines with the ELISAs performed on the sera detecting anti-LPS IgG, anti-flagella IgG or IgM (p = 0.017, 0.017 and p < 0.001 respectively). When comparing the kinetics of the selected ELISAs, the IgG antibodies against LPS detected between-line variations as early as 1 to 4 weeks pi, whereas with IgG against flagella, the differences were only detected at 1 and 2 weeks pi and with IgM against flagella, the differences were significant at 1, 2, 4 and 8 weeks pi. In conclusion, resistant hen lines producing higher levels of antibodies than the susceptible hen lines may be selected with these ELISAs.

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“…A biallelic phenotype in mouse, termed Ity/Lsh/Bcg, was identified in response to infection by obligate intracellular macrophage pathogens (1)(2)(3). Nramp1 1 (also termed Slc11a1) was isolated as the positional gene candidate for Ity/Lsh/Bcg (4).…”

mentioning

confidence: 99%

c-Myc Represses and Miz-1 Activates the Murine Natural Resistance-associated Protein 1 Promoter

Bowen¹,

Biggs²,

Phillips³

et al. 2002

Journal of Biological Chemistry

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Iron is essential for growth, and impaired iron homoeostasis through a non-conserved mutation within murine Nramp1, also termed Slc11a1, contributes to susceptibility to infection. Nramp1 depletes the macrophage cytosol of iron, with effects on iron-regulated gene expression and iron-dependent processes. Wu and colleagues (Wu, K.-J., Polack, A., and Dalla-Favera, R. A biallelic phenotype in mouse, termed Ity/Lsh/Bcg, was identified in response to infection by obligate intracellular macrophage pathogens (1-3). Nramp1 1 (also termed Slc11a1) was isolated as the positional gene candidate for Ity/Lsh/Bcg (4). In subsequent studies the full-length sequence of the encoded polypeptide was identified (5). Mouse strains resistant to infection encode Gly at codon 169 within Nramp1 whereas susceptible mice encode Asp (6). The G169D polymorphism is sufficient to explain the outcomes of model infections within inbred mouse strains at pre-T cell stages of infection, as confirmed by gene targeting and transgenesis experiments (7,8).Allele D169 is phenotypically null (7). When Nramp1 was cloned, the biochemical basis for its control over the proliferation of intracellular pathogens was not obvious, but the sequence suggested a transporter function (4). Subsequent studies showed the encoded polytopic integral membrane Nramp1 protein was expressed in a perinuclear location, on intracellular late endosomal/lysosomal membranes (9 -11). Nramp1 underwent rapid recruitment to the periphery of a pathogencontaining vesicle (10, 11) and displayed a more peripheral location in response to treatment with interferon-␥ (11). These observations led to the suggestion that growth control of microbial pathogens could be achieved by the transport of some toxin into the lumen of the phagosome or by the sequestration of some essential nutrient. The identity of a candidate transport substrate was revealed from studies on a highly sequencerelated gene, Nramp2 (DMT1/DCT1/SLC11A2). Nramp2 was initially isolated as an orphan gene (12) but was re-isolated by functional cloning through a divalent cation/iron uptake assay (13). In addition, identical mutations, G185R, within Nramp2 in the mk mouse and the Belgrade rat are associated with impaired intestinal and erythroid cell iron uptake (14). Based on the striking sequence similarity between the two polypeptides (15), Nramp1 was also predicted to transport divalent cations or iron within murine macrophages, and infection susceptibility occurs through impaired divalent cation transport. The many pleiotropic effects attributed to Nramp1 (16) should be explained by differential cation transport. Because Nramp1 protein is expressed within internal membranes, the differential partitioning of divalent cations between the cytosol and the lumen of the internal vesicle should contribute to the pleiotropic effects described (16). Inducible nitric-oxide synthase (iNos) is expressed at quantitatively higher levels in functional-Nramp1 macrophages (17)(18)(19)(20). Ferrous iron provides the link between iNos expressio...

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Natural resistance to Salmonella infection, delayed hypersensitivity and Ir genes in different strains of mice

Cited by 136 publications

References 8 publications

Immunolocalisation of theD. melanogaster NramphomologueMalvolioto gut and Malpighian tubules provides evidence thatMalvolioandNramp2are orthologous

Immunolocalisation of theD. melanogaster NramphomologueMalvolioto gut and Malpighian tubules provides evidence thatMalvolioandNramp2are orthologous

Reliable ELISAs showing differences between resistant and susceptible lines in hens orally inoculated with Salmonella Enteritidis

c-Myc Represses and Miz-1 Activates the Murine Natural Resistance-associated Protein 1 Promoter

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