title: Immune and biochemical responses in skin differ between bovine hosts genetically susceptible and resistant to the cattle tick Rhipicephalus microplus.
abstract: Ticks attach to and penetrate their hosts' skin and inactivate multiple components of host responses in order to acquire a blood meal. Infestation loads with the cattle tick, Rhipicephalus microplus, are heritable: some breeds carry high loads of reproductively successful ticks, whereas in others, few ticks feed and reproduce efficiently.
  
  
  
  In order to elucidate the mechanisms that result in the different outcomes of infestations with cattle ticks, we examined global gene expression and inflammation induced by tick bites in skins from one resistant and one susceptible breed of cattle that underwent primary infestations with larvae and nymphs of R. microplus. We also examined the expression profiles of genes encoding secreted tick proteins that mediate parasitism in larvae and nymphs feeding on these breeds.
  
  
  
  Functional analyses of differentially expressed genes in the skin suggest that allergic contact-like dermatitis develops with ensuing production of IL-6, CXCL-8 and CCL-2 and is sustained by HMGB1, ISG15 and PKR, leading to expression of pro-inflammatory chemokines and cytokines that recruit granulocytes and T lymphocytes. Importantly, this response is delayed in susceptible hosts. Histopathological analyses of infested skins showed inflammatory reactions surrounding tick cement cones that enable attachment in both breeds, but in genetically tick-resistant bovines they destabilized the cone. The transcription data provided insights into tick-mediated activation of basophils, which have previously been shown to be a key to host resistance in model systems. Skin from tick-susceptible bovines expressed more transcripts encoding enzymes that detoxify tissues. Interestingly, these enzymes also produce volatile odoriferous compounds and, accordingly, skin rubbings from tick-susceptible bovines attracted significantly more tick larvae than rubbings from resistant hosts. Moreover, transcripts encoding secreted modulatory molecules by the tick were significantly more abundant in larval and in nymphal salivary glands from ticks feeding on susceptible bovines.
  
  
  
  Compared with tick-susceptible hosts, genes encoding enzymes producing volatile compounds exhibit significantly lower expression in resistant hosts, which may render them less attractive to larvae; resistant hosts expose ticks to an earlier inflammatory response, which in ticks is associated with significantly lower expression of genes encoding salivary proteins that suppress host immunity, inflammation and coagulation.
authors.affiliation: Departament of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil.
authors.forename: Alessandra Mara
authors.initials: AM
authors.lastname: Franzin
authors.affiliation: Departament of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil.|Department of Genetics and Evolution, Federal University of São Carlos, São Carlos, SP, 13565-905, Brazil.
authors.forename: Sandra Regina
authors.initials: SR
authors.lastname: Maruyama
authors.affiliation: Departament of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil.
authors.forename: Gustavo Rocha
authors.initials: GR
authors.lastname: Garcia
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.|Integrative Medicine Program, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.
authors.forename: Rosane Pereira
authors.initials: RP
authors.lastname: Oliveira
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: José Marcos Chaves
authors.initials: JM
authors.lastname: Ribeiro
authors.affiliation: International Livestock Research Institute, Nairobi, Kenya.|Embrapa Pecuária Sudeste, São Carlos, SP, 13560-970, Brazil.
authors.forename: Richard
authors.initials: R
authors.lastname: Bishop
authors.affiliation: Department of Basic Sciences, School of Animal Science and Food Technology, University of São Paulo, Pirassununga, SP, 13635-900, Brazil.
authors.forename: Antônio Augusto Mendes
authors.initials: AA
authors.lastname: Maia
authors.affiliation: Departament of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil.|Department of Veterinary Microbiology & Pathology, Washington State University, Pullman, WA, 99164-7040, USA.
authors.forename: Daniela Dantas
authors.initials: DD
authors.lastname: Moré
authors.affiliation: Ribeirão Preto School of Nursing, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Beatriz Rossetti
authors.initials: BR
authors.lastname: Ferreira
authors.affiliation: Departament of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil. imsantos@fmrp.usp.br.
authors.forename: Isabel Kinney Ferreira de Miranda
authors.initials: IK
authors.lastname: Santos
mesh_terms: D000818:Animals; D060829:Arthropod Proteins / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D016207:Cytokines / Q000235:genetics; D003872:Dermatitis / Q000235:genetics / Q000276:immunology / Q000469:parasitology / Q000662:veterinary; D004198:Disease Susceptibility / Q000469:parasitology; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006790:Host-Parasite Interactions / Q000235:genetics / Q000276:immunology; D007249:Inflammation / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007814:Larva / Q000502:physiology; D009758:Nymph / Q000502:physiology; D048494:Rhipicephalus / Q000276:immunology*; D012867:Skin / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D013984:Tick Infestations / Q000235:genetics / Q000276:immunology / Q000662:veterinary*
chemical_list: D060829:Arthropod Proteins; D016207:Cytokines; D015850:Interleukin-6
keywords: Bos indicus; Bos taurus; Differentially expressed genes; Rhipicephalus microplus; Salivary glands; Skin; Transcriptome