Protective Effect of the Nramp1 BB Genotype against<i>Brucella abortus</i>in the Water Buffalo (<i>Bubalus bubalis</i>)

Capparelli, Rosanna; Alfano, Flora; Amoroso, Maria Grazia; Borriello, Giorgia; Fenizia, D.; Bianco, A T; Roperto, Sante; Roperto, F.; Iannelli, Domenico

doi:10.1128/iai.00948-06

Cited by 48 publications

(40 citation statements)

References 38 publications

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“…The highest gene expression level was recorded in the infected carriers of the (GT) 16 allele. In another study, Capparelli et al (2007a) confirmed that non-infected (GT) 16 monocytes exhibited a basal level of SLC11A1 expression that was approximately five times higher than those of non-infected (GT) 12 monocytes. Moreover, both infected and non-infected (GT) 16 monocytes exhibited significantly higher reactive oxygen intermediate generation than did monocytes from carriers of other alleles.…”

Section: Discussionsupporting

confidence: 60%

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Analysis of SLC11A1 gene expression in healthy water buffalo (Bubalus bubalis) blood cells using qPCR

Crisà¹,

Matteis²,

Scatà³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. SLC11A1 (solute carrier family 11 member 1 protein) gene influences the initial phase of bacterial cellular infections through macrophage activation. Recent literature on buffalo has attempted to associate the genotype of the polymorphic microsatellite located in the 3ꞌuntranslated region (3ꞌUTR) of the gene, with either susceptibility to brucellosis or with improved macrophage function. Carriers of the (GT) 16 allele have been reported to be resistant to brucellosis. In this study we analyzed the steady-state level of SLC11A1 expression in a serologically negative herd of 26 animals differing by the number of (GT) n microsatellite repeats by using a reverse transcriptase quantitative real-time polymerase chain reaction approach. We evaluated five different reference genes, which had not been reported previously, for use in gene expression experiments in buffalo blood. However, we did not find any significant difference between buffalo carriers of the different microsatellite alleles, with respect to SLC11A1 expression in whole blood or in blood fractions [peripheral blood mononuclear cells (PBMC) and polymorphonuclear leukocytes/granulocytes (PMN/G)]. Conversely, there was a difference between the blood fractions in their SLC11A1 expression levels, with the PMN/G fraction having a higher expression level than the PBMC fraction (P < 0.015).

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Section: Discussionsupporting

confidence: 60%

“…Alleles (GT) 16 and (GT) 12 are present in the first block and correspond to the alleles reported by Capparelli et al (2007a) as B (DQ095781) and A (DQ095780), respectively. The second block present (GT) 14 and (GT) 15 repeats, respectively.…”

Section: Resultsmentioning

confidence: 99%

Analysis of SLC11A1 gene expression in healthy water buffalo (Bubalus bubalis) blood cells using qPCR

Crisà¹,

Matteis²,

Scatà³

et al. 2013

Genet. Mol. Res.

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“…Studies have shown, however, that Nramp1 does not play a prominent role in protecting experimentally infected mice from Brucella infections (33). Studies of ruminants have also shown that the contributions of this divalent cation transporter to host defense against Brucella infections vary depending on the species of ruminant being examined (10,54). Thus, the severe attenuation exhibited by the B. abortus mntH mutant in C57BL/6 mice (which lack a functional Nramp1) (67) and cultivated macrophages obtained from these mice is particularly striking.…”

Section: Discussionmentioning

confidence: 99%

The Manganese Transporter MntH Is a Critical Virulence Determinant forBrucella abortus2308 in Experimentally Infected Mice

et al. 2009

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The gene designated BAB1_1460 in the Brucella abortus 2308 genome sequence is predicted to encode the manganese transporter MntH. Phenotypic analysis of an isogenic mntH mutant indicates that MntH is the sole high-affinity manganese transporter in this bacterium but that MntH does not play a detectable role in the transport of Fe 2؉ , Zn 2؉ , Co 2؉ , or Ni 2؉ . Consistent with the apparent selectivity of the corresponding gene product, the expression of the mntH gene in B. abortus 2308 is repressed by Mn 2؉ , but not Fe 2؉ , and this Mn-responsive expression is mediated by a Mur-like repressor. The B. abortus mntH mutant MWV15 exhibits increased susceptibility to oxidative killing in vitro compared to strain 2308, and a comparative analysis of the superoxide dismutase activities present in these two strains indicates that the parental strain requires MntH in order to make wild-type levels of its manganese superoxide dismutase SodA. The B. abortus mntH mutant also exhibits extreme attenuation in both cultured murine macrophages and experimentally infected C57BL/6 mice. These experimental findings indicate that Mn 2؉ transport mediated by MntH plays an important role in the physiology of B. abortus 2308, particularly during its intracellular survival and replication in the host.Brucella abortus is a gram-negative bacterium that is responsible for the zoonotic disease brucellosis. Brucellosis causes spontaneous abortion and sterility in ruminants (27) and a debilitating febrile illness in humans known as undulant fever (17). The ability of brucellae to cause disease is directly related to their capacity to establish and maintain intracellular infection in host macrophages (63). Within the phagosomal compartment in these host cells, brucellae must cope with oxidative stress, low pH, and nutrient deprivation. The availability of metal ions is restricted within this environment due in part to the activity of the host natural resistance-associated macrophage protein (NRAMP-1), which transports divalent cations out of the phagosome (40). Mn 2ϩ serves as an important cofactor for a variety of bacterial enzymes, including those involved in carbon metabolism, induction of the stringent response, and detoxification of reactive oxygen species (ROS) (55). Consequently, the inability of brucellae to acquire sufficient levels of this divalent cation may compromise their ability to successfully adapt to the environmental conditions encountered during residence in their intracellular niche.Manganese uptake by bacteria is typically accomplished through the activity of either ABC-type transporters such as the SitABC complex (4, 42, 59, 65) or H ϩ -dependent manganese transporters such as MntH (37, 41, 52, 60). Many bacteria possess both types of Mn 2ϩ transporters (55), but a survey of the publicly available Brucella genome sequences (14,20,36,57) suggests that these bacteria do not produce a SitABC-type transporter and rely solely on an MntH homolog for the highaffinity transport of Mn 2ϩ . Escherichia coli MntH was originally des...

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“…and Leishmania sp. (Vidal et al, 1995;Gruenheid et al, 1997;Zwilling et al, 1999;Jabado et al, 2000;Capparelli et al, 2007). The function of Nramp1 in virus infection has not yet been elucidated, but its about 8-fold upregulation in PBLs following CSFV infection indicates that it is possibly involved in the anti-CSFV cellular response.…”

Section: Discussionmentioning

confidence: 99%

Genomic expression profiling of peripheral blood leukocytes of pigs infected with highly virulent classical swine fever virus strain Shimen

Shi

Sun

Guo

et al. 2009

Journal of General Virology

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Classical swine fever (CSF), caused by a virus of the same name (CSFV), is a highly contagious swine pyrexic disease featuring extensive haemorrhagic lesions and leukopenia, but little is known about the molecular mechanisms of its pathogenesis. To gain insight into the interaction between the virus and host cells, microarray analyses were performed to detect alterations in genomic expression of pig peripheral blood leukocytes (PBLs) following CSFV infection. Three healthy pigs were inoculated with a lethal dose of highly virulent CSFV strain Shimen. PBLs were isolated at the onset of typical clinical signs and total RNA was subjected to microarray analyses with Affymetrix Porcine Genome Array GeneChips. Of all 20 201 pig genes arrayed in the chip, 1745 showed altered expression (up-or downregulation) after infection. These were classified into eight functional groups, relating to cell proliferation (3.6 %), immune response (2.1 %), apoptosis (1.4 %), kinase activity (1.4 %), signal transduction (1.4 %), transcription (0.7 %), receptor activity (0.7 %) and cytokines/chemokines (0.4 %). The remaining 88.3 % of genes had unknown functions. Alterations in genomic expression were confirmed by real-time RT-PCR of selected cellular genes and Western blotting of annexin 2, a cellular protein relating to virus infection. The observed expression changes of numerous genes involved in immune and inflammatory responses and in the apoptosis process indicate that CSFV has developed sophisticated mechanisms to cause leukopenia in infected pigs. These data provide a basis for exploring the molecular pathogenesis of CSFV infection through an understanding of the interaction between viral and cellular components. INTRODUCTIONClassical swine fever virus (CSFV) is a small, enveloped virus with a positive-stranded RNA genome that belongs in the genus Pestivirus, together with two bovine viral diarrhea virus species and border disease virus, within the family Flaviviridae (Thiel et al., 2004). The virus genome is approximately 12.5 kb in size and contains a single, large open reading frame that encodes a 3898 aa polyprotein (Meyers et al., 1999).CSFV has a particular tropism for cells of the immune system and is known to cause severe leukopenia, in particular lymphopenia, featuring atrophy of primary lymphoid tissue (van der Molen & van Oirschot, 1981) and bone marrow (Summerfield et al., 2000), and depletion of different subsets of leukocytes (T and B lymphocytes, monocytes-macrophages and granulocytes) in infected pigs (Summerfield et al., 1998(Summerfield et al., , 2000(Summerfield et al., , 2001aCarrasco et al., 2004;von Freyburg et al., 2004). All leukocytes are depleted during CSFV infection, but B lymphocytes are particularly susceptible (Susa et al., 1992). Besides the reduction in leukocyte numbers, lymphocyte activation and function during virulent CSFV infection are impaired severely, thereby significantly decreasing antibody production and host defences (Lee et al., 1999). The destruction of leukocytes following CSFV infe...

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Protective Effect of the Nramp1 BB Genotype againstBrucella abortusin the Water Buffalo (Bubalus bubalis)

Cited by 48 publications

References 38 publications

Analysis of SLC11A1 gene expression in healthy water buffalo (Bubalus bubalis) blood cells using qPCR

Analysis of SLC11A1 gene expression in healthy water buffalo (Bubalus bubalis) blood cells using qPCR

The Manganese Transporter MntH Is a Critical Virulence Determinant forBrucella abortus2308 in Experimentally Infected Mice

Genomic expression profiling of peripheral blood leukocytes of pigs infected with highly virulent classical swine fever virus strain Shimen

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