The mouse gene Nramp1 (natural resistance-associated macrophage protein) confers resistance to some intracellular pathogens, such as Mycobacterium bovis, Salmonella tiphimurium and Leishmania donovani (Govoni G. and Gros P. 1998. Macrophage Nramp1 and its role in resistance to microbial infections. Inflamm. Res., 47:277-284). In cattle, this gene is associated with resistance to Brucella abortus (Barthel B. et al., 2001 Stable trasfection of the bovine Nramp1 gene into murine RAW264.7 cells: effects on Brucella abortus survival. Infect. Immun. 69:3110-3119). These studies have shown that the Nramp1 gene plays a critical role in determining natural resistance to intracellular infections, though its mechanism of action has not yet been fully clarified (Nramp1 acts in the intracellular transport of bivalent Fe++ ions and other cations). Scientific studies on the natural resistance of the Mediterranean buffalo to brucellosis have shown that resistance is associated with the presence of the Nramp1 gene in homozygous (Borriello G. et al., 2006. Genetic resistance to Brucella abortus in Water Buffalo (Bubalis Bubalis). Infect. Immun. 74:2115-2120), and particularly with the homozygous presence of the BB allele. In this regard, it has been demonstrated that a large quantity of Nramp1mRNA and a low number of active bacteria are present within buffalo monocytes that are positive for the BB allele (Capparelli R., et al. 2006. Protective effect of the Nramp1 BB genotype against Brucella abortus in Water Buffalo (Bubalus Bubalis) Infect. Immun.). Comparison of these data with the corresponding values observed in monocytes positive for the AA allele reveals marked differences; for this reason, the presence of the AA allele has been associated with poor resistance. In addition to the Nramp1 gene, those genes that are associated with expression of the major histocompatibility complex (MHC) are in some way connected with disease resistance. These genes codify for glycoprotein receptors that present the antigen to the T-lymphocytes, thereby eliciting a specific immune response. The project aims to demonstrate that the Nramp1 gene and the genes codifying for the MHC are associated with the natural resistance of the Mediterranean buffalo to infection by Brucella abortus. To this end, a test of infection in controlled conditions is to be performed both on a group of Mediterranean buffaloes that are "presumably resistant" and on a control group. Indeed, while the studies conducted so far have ascertained such an association, no experimental infection tests able to provide scientific evidence of the strength of the phenomenon have yet been carried out. Moreover, the project aims to search for and identify further genes responsible for protecting the buffalo against Brucella abortus. The intention here is to pave the way towards a clearer policy with regard to the possible practical exploitation of the phenomenon for purposes of prophylaxis and eradication of the disease (e.g. genetic selection of resistant animals, infection-site management, etc) as an adjunct to traditional preventive measures.

VERIFICATION OF THE EFFICACYOF THE PROTECTIVE ACTION OF GENES CONFERRING RESISTANCE TO INFECTIONBY BRUCELLA ABORTUS IN THE MEDITERRANEAN BUFFALO / Pagnini, Ugo. - (2009).

VERIFICATION OF THE EFFICACYOF THE PROTECTIVE ACTION OF GENES CONFERRING RESISTANCE TO INFECTIONBY BRUCELLA ABORTUS IN THE MEDITERRANEAN BUFFALO

PAGNINI, UGO
2009

Abstract

The mouse gene Nramp1 (natural resistance-associated macrophage protein) confers resistance to some intracellular pathogens, such as Mycobacterium bovis, Salmonella tiphimurium and Leishmania donovani (Govoni G. and Gros P. 1998. Macrophage Nramp1 and its role in resistance to microbial infections. Inflamm. Res., 47:277-284). In cattle, this gene is associated with resistance to Brucella abortus (Barthel B. et al., 2001 Stable trasfection of the bovine Nramp1 gene into murine RAW264.7 cells: effects on Brucella abortus survival. Infect. Immun. 69:3110-3119). These studies have shown that the Nramp1 gene plays a critical role in determining natural resistance to intracellular infections, though its mechanism of action has not yet been fully clarified (Nramp1 acts in the intracellular transport of bivalent Fe++ ions and other cations). Scientific studies on the natural resistance of the Mediterranean buffalo to brucellosis have shown that resistance is associated with the presence of the Nramp1 gene in homozygous (Borriello G. et al., 2006. Genetic resistance to Brucella abortus in Water Buffalo (Bubalis Bubalis). Infect. Immun. 74:2115-2120), and particularly with the homozygous presence of the BB allele. In this regard, it has been demonstrated that a large quantity of Nramp1mRNA and a low number of active bacteria are present within buffalo monocytes that are positive for the BB allele (Capparelli R., et al. 2006. Protective effect of the Nramp1 BB genotype against Brucella abortus in Water Buffalo (Bubalus Bubalis) Infect. Immun.). Comparison of these data with the corresponding values observed in monocytes positive for the AA allele reveals marked differences; for this reason, the presence of the AA allele has been associated with poor resistance. In addition to the Nramp1 gene, those genes that are associated with expression of the major histocompatibility complex (MHC) are in some way connected with disease resistance. These genes codify for glycoprotein receptors that present the antigen to the T-lymphocytes, thereby eliciting a specific immune response. The project aims to demonstrate that the Nramp1 gene and the genes codifying for the MHC are associated with the natural resistance of the Mediterranean buffalo to infection by Brucella abortus. To this end, a test of infection in controlled conditions is to be performed both on a group of Mediterranean buffaloes that are "presumably resistant" and on a control group. Indeed, while the studies conducted so far have ascertained such an association, no experimental infection tests able to provide scientific evidence of the strength of the phenomenon have yet been carried out. Moreover, the project aims to search for and identify further genes responsible for protecting the buffalo against Brucella abortus. The intention here is to pave the way towards a clearer policy with regard to the possible practical exploitation of the phenomenon for purposes of prophylaxis and eradication of the disease (e.g. genetic selection of resistant animals, infection-site management, etc) as an adjunct to traditional preventive measures.
2009
VERIFICATION OF THE EFFICACYOF THE PROTECTIVE ACTION OF GENES CONFERRING RESISTANCE TO INFECTIONBY BRUCELLA ABORTUS IN THE MEDITERRANEAN BUFFALO / Pagnini, Ugo. - (2009).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/377243
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