MYD88 and functionally related genes are associated with multiple infections in a model population of Kenyan village dogs
- 267 Downloads
The purpose of this study was to seek associations between immunity-related molecular markers and endemic infections in a model population of African village dogs from Northern Kenya with no veterinary care and no selective breeding. A population of village dogs from Northern Kenya composed of three sub-populations from three different areas (84, 50 and 55 dogs) was studied. Canine distemper virus (CDV), Hepatozoon canis, Microfilariae (Acantocheilonema dracunculoides, Acantocheilonema reconditum) and Neospora caninum were the pathogens studied. The presence of antibodies (CDV, Neospora), light microscopy (Hepatozoon) and diagnostic PCR (Microfilariae) were the methods used for diagnosing infection. Genes involved in innate immune mechanisms, NOS3, IL6, TLR1, TLR2, TLR4, TLR7, TLR9, LY96, MYD88, and three major histocompatibility genes class II genes were selected as candidates. Single nucleotide polymorphism (SNP) markers were detected by Sanger sequencing, next generation sequencing and PCR-RFLP. The Fisher´s exact test for additive and non-additive models was used for association analyses. Three SNPs within the MYD88 gene and one TLR4 SNP marker were associated with more than one infection. Combined genotypes and further markers identified by next generation sequencing confirmed associations observed for individual genes. The genes associated with infection and their combinations in specific genotypes match well our knowledge on their biological role and on the role of the relevant biological pathways, respectively. Associations with multiple infections observed between the MYD88 and TLR4 genes suggest their involvement in the mechanisms of anti-infectious defenses in dogs.
KeywordsKenyan village dogs Immunity-related genes Associations Infectious diseases
This work was supported by the Central European Institute of Technology (CEITEC) CZ.1.05/1.1.00/02.0068 and by the project IGA VFU 157/2008/FVL.
- 11.Dutra MS, Bela SR, Peixoto-Rangel AL, Fakiola M, Cruz AG, Gazzinelli A, Quites HF, Bahia-Oliveira LM, Peixe RG, Campos WR, Higino-Rocha AC, Miller NE, Blackwell JM, Antonelli LR, Gazzinelli RT (2013) Association of a NOD2 gene polymorphism and T-helper 17 cells with presumed ocular toxoplasmosis. J Infect Dis 207:152–163CrossRefPubMedGoogle Scholar
- 26.Albrechtova K (2008) Blood parasites in Samburu dogs. Thesis. University of Veterinary and Pharmaceutical Sciences Brno, Faculty of Veterinary Medicine, p 76Google Scholar
- 29.Boyko AR, Boyko RH, Boyko CM, Parker HG, Castelhano M, Corey L, Degenhardt JD, Auton A, Hedimbi M, Kityo R, Ostrander EA, Schoenebeck J, Todhunter RJ, Jones P, Bustamante CD (2009) Complex population structure in African village dogs and its implications for inferring dog domestication history. PNAS 106:13903–13908CrossRefPubMedPubMedCentralGoogle Scholar
- 32.D’Agostino RB, Chase W, Belanger A (1988) The appropriateness of some common procedures for testing the equality of two independent binomial populations. Am Stat 42:198–202Google Scholar
- 34.Zar JH (1999) Biostatical analysis, 4th edn. Prentice Hall, Upper Saddle River, p 662Google Scholar
- 40.Clayton DG, Walker NM, Smyth DJ, Pask R, Cooper JD, Maier LM, Smink LJ, Lam AC, Ovington NR, Stevens HE, Nutland S, Howson JM, Faham M, Moorhead M, Jones HB, Falkowski M, Hardenbol P, Willis TD, Todd JA (2005) Population structure, differential bias and genomic control in a large-scale, case-control association study. Nat Genet 37:1243–1246CrossRefPubMedGoogle Scholar
- 42.Qeska V, Barthel Y, Herder V, Stein VM, Tipold A, Urhausen C, Günzel-Apel AR, Rohn K, Baumgärtner W, Beineke A (2014) Canine distemper virus infection leads to an inhibitory phenotype of monocyte-derived dendritic cells in vitro with reduced expression of co-stimulatory molecules and increased interleukin-10 transcription. PLoS One. doi: 10.1371/journal.pone.0096121 PubMedPubMedCentralGoogle Scholar
- 44.Albiger B, Sandgren A, Katsuragi H, Meyer-Hoffert U, Beiter K, Wartha F, Hornef M, Normark S, Normark BH (2005) Myeloid differentiation factor 88-dependent signalling controls bacterial growth during colonization and systemic pneumococcal disease in mice. Cell Microbiol 7:1603–1615CrossRefPubMedGoogle Scholar
- 45.Seki E, Tsutsui H, Tsuji NM, Hayashi N, Adachi K, Nakano H, Futatsugi-Yumikura S, Takeuchi O, Hoshino K, Akira S, Fujimoto J, Nakanishi K (2002) Critical roles of myeloid differentiation factor 88-dependent proinflammatory cytokine release in early phase clearance of Listeria monocytogenes in mice. J Immunol 169:3863–3868CrossRefPubMedGoogle Scholar
- 47.Delale T, Paquin A, Asselin-Paturel C, Dalod M, Brizard G, Bates EE, Kastner P, Chan S, Akira S, Vicari A, Biron CA, Trinchieri G, Brière F (2005) MyD88-dependent and -independent murine cytomegalovirus sensing for IFN-alpha release and initiation of immune responses in vivo. J Immunol 175:6723–6732CrossRefPubMedGoogle Scholar