Tryptophan metabolism and resistance to tick infestations

• Grant number: 12/14995-1
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2013
• End date: May 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Isabel Kinney Ferreira de Miranda Santos
• Grantee: Isabel Kinney Ferreira de Miranda Santos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Alexandre Rodrigues Caetano ; Cecília José Veríssimo ; Luiz Alberto Beraldo de Moraes

Abstract

Metabolites of non-protein tryptophan (TRY) metabolism affect neurological, immunological and semiochemical processes in arthropods and in vertebrates. However, nothing is known about their role in ticks and in skin reactions of hosts to tick bites. In order to elucidate mechanisms of immunity to ticks we exploit a model of contrasting phenotypes of infestations presented by different breeds of bovines in which global gene expression was profiled in non-infested and tick-infested skin. Functional analysis with Metacore of the differentially expressed genes indicated that metabolism of TRY is a very significant component of both the local reaction to tick bites in skin and the outcome presented by the extreme phenotypes of infestations. In this project we will confirm and elucidate the role of TRY metabolism in tick infestations in our model. For this we will quantify expression of candidate genes in skin and in blood leukocytes of artificially infested bovines with a custom PCR array curated with Metacore and mining of relevant literature. We will measure TRY metabolites in skin, urine and blood from tick-free and infested animals and characterize chemical components from skin rubbings. We will also interfere in selected points of TRY metabolism and then measure in non-infested and artificially infested bovines: the metabolic outcome in skin, urine and blood; the outcome of infestations; the outcome of the hair follicle cycle; expression of candidate genes; skin inflammation. From crosses between breeds presenting extreme phenotypes (Girolandos) we will also sequence PCR products of the top genes determined in the gene expressions studies. We will then look for single nucleotide polymorphisms in these products and examine if they are associated with phenotypes of infestations, levels of TRY metabolites and production of semiochemicals. We expect to provide evidence that TRY metabolism has a role in resistance to tick infestations. (AU)