Trypanotolerance In Cattle Research Articles

Computational Identification of Master Regulators Influencing Trypanotolerance in Cattle.

African Animal Trypanosomiasis (AAT) is transmitted by the tsetse fly which carries pathogenic trypanosomes in its saliva, thus causing debilitating infection to livestock health. As the disease advances, a multistage progression process is observed based on the progressive clinical signs displayed in the host’s body. Investigation of genes expressed with regular monotonic patterns (known as Monotonically Expressed Genes (MEGs)) and of their master regulators can provide important clue for the understanding of the molecular mechanisms underlying the AAT disease. For this purpose, we analysed MEGs for three tissues (liver, spleen and lymph node) of two cattle breeds, namely trypanosusceptible Boran and trypanotolerant N’Dama. Our analysis revealed cattle breed-specific master regulators which are highly related to distinguish the genetic programs in both cattle breeds. Especially the master regulators MYC and DBP found in this study, seem to influence the immune responses strongly, thereby susceptibility and trypanotolerance of Boran and N’Dama respectively. Furthermore, our pathway analysis also bolsters the crucial roles of these master regulators. Taken together, our findings provide novel insights into breed-specific master regulators which orchestrate the regulatory cascades influencing the level of trypanotolerance in cattle breeds and thus could be promising drug targets for future therapeutic interventions.

Packed cell volume and bone marrow cytological responses in Trypanosoma vivax-induced acute trypanosomosis in Nigerian Sokoto Red goats

Bone marrow responses have been identified as key determinants of trypanotolerance in cattle as they determine the ability for hemopoietic cell regeneration and control of anemia. However, not much is known about such responses in Nigerian breed of goats known to show different susceptibilities to trypanosome infections. Early bone marrow events associated with pathogenesis of Sokoto Red goats to Trypanosoma vivax were investigated in six goats to assess their role in susceptibility of this goat breed to trypanosomiasis. A total of six Sokoto Red goats of mixed sexes were used. While four of the goats randomly selected were infected with Trypanosoma vivax, the remaining two served as control. The parameters examined included packed cell volume (PCV) and differential bone marrow cytology. Cytological changes in the bone marrow of goats with acute trypanosomosis were compared to the controls. T. vivax caused an acute disease course in the goats resulting to mild drop in PCV and death 2–3 weeks post infection (PI). Associated bone marrow (BM) cytological changes were characterized by moderate erythroid hyperplasia with a resultant lower myeloid:erythroid (M:E) ratio, while the granulocytic maturation rate was 3.15 ± 0.6 and 2.42 ± 0.0 for infected and control animals, respectively. However, significant macrophage (MC) numbers (hyperplasia) were detected in the BM of the infected group. Most of the MCs phagocytized mature red blood cells (RBC) and band or mature white blood cells (WBC) only while no MC phagocytized immature cells. The MCs in BM of control goats phagocytized no blood cells. The study confirmed that mature blood cells form the first cell types to be phagocytized by MCs of BM in the pathogenesis of anemia in T. vivax-infected Sokoto Red goats while early onset of MC hyperplasia and erythrophagocytosis are indicators of susceptibility to trypanosomosis in this breed of goats and perhaps other susceptible ruminants.

Lack of haplotype structuring for two candidate genes for trypanotolerance in cattle.

Bovine trypanotolerance is a heritable trait associated to the ability of the individuals to control parasitaemia and anaemia. The INHBA (BTA4) and TICAM1 (BTA7) genes are strong candidates for trypanotolerance-related traits. The coding sequence of both genes (3951bp in total) were analysed in a panel including 79 Asian, African and European cattle (Bos taurus and B. indicus) to identify naturally occurring polymorphisms on both genes. In general, the genetic diversity was low. Nineteen of the 33 mutations identified were found just one time. Seventeen different haplotypes were defined for the TICAM1 gene, and 9 and 12 were defined for the exon 1 and the exon 2 of the INHBA gene, respectively. There was no clear separation between cattle groups. The most frequent haplotypes identified in West African taurine samples were also identified in other cattle groups including Asian zebu and European cattle. Phylogenetic trees and principal component analysis confirmed that divergence among the cattle groups analysed was poor, particularly for the INHBA sequences. The European cattle subset had the lowest values of haplotype diversity for both the exon1 (monomorphic) and the exon2 (0.077±0.066) of the INHBA gene. Neutrality tests, in general, did not suggest that the analysed genes were under positive selection. The assessed scenario would be consistent with the identification of recent mutations in evolutionary terms.

Trypanotolerance in small ruminants of sub-Saharan Africa

Although a lot of information is currently available on trypanotolerance in cattle, until recently the trypanotolerant nature of small ruminants was not well known. Trypanotolerance in small ruminants is less pronounced than in cattle and should be considered as resilience rather than resistance. West African Dwarf (WAD) goats seem to be less trypanotolerant than Djallonke sheep. However, recent studies have shown that there is an important introgression of genes of trypanosusceptible breeds into WAD goat populations, which possibly explains the loss of trypanotolerance in these animals. Measures need to be taken to safeguard and upgrade the genetic purity of trypanotolerant goat and sheep breeds in Africa.

The Genetics of Trypanotolerance in Cattle: A Review

Trypanosomosis is a major recognized factor limiting livestock productivity. Control of the disease has explored the use of drugs, vector and the farming of trypanotolerant livestock in order to enhance productivity. However, there are documented difficulties with each of the methods. These include drug resistance, re-invasion of controlled areas by tsetse flies and the small population of the trypanotolerant cattle population. Hence the search for genes that will confer trypanosome-resistance and enhance productivity is imperative. Attempts to control trypanosomosis using molecular genetic techniques have continued over the years. In this brief review, the advances made towards an understanding of genetics involved in trypanotolerance will be highlighted. So far, the genome involved in the genetics of trypanotolerance in cattle and in mice, known as the quantitative trait loci (QTL), has been identified using microsattelites. Comparative studies of map data between cattle and mice in the principal QTL region of both species have revealed a region of homology of about 300,000 base pairs (bp) between cattle chromosome 7 and mouse chromosome 17 lying within the principal QTL in both species. This finding points to the possibility that the underlying genes in these two QTL could be the same in cattle and mice and may pave the way for the eventual identification of trypanotolerant genes. The identification of the genes would make it possible to use transgenic approaches that would incorporate resistance to trypanosomosis for control design. Keywords: Genetics, trypanotolerance, cattle Trop. Vet. Vol. 21 (2) 55-60 (2003)

Trypanotolerance, an option for sustainable livestock production in areas at risk from trypanosomosis.

Trypanosomosis is one of the major constraints on animal production in areas of Africa which have the greatest potential for significant increases in domestic livestock populations and livestock productivity. While the eradication of trypanosomosis from the entire continent is an unrealistic goal, considerable effort has been invested in the control of this disease through the use of trypanocidal drugs, management of the vector and exploitation of the genetic resistance exhibited by indigenous breeds. There is little hope that a conventional, anti-infection vaccine will be produced in the near future. Drug resistance is developing faster than generally thought. The control of the tsetse fly has been attempted over many decades. The decreasing efficacy of available trypanocidal drugs and the difficulties of sustaining tsetse control increase the imperative need to enhance trypanotolerance through selective breeding, either within breeds or through cross-breeding. Trypanotolerance has been defined as the relative capacity of an animal to control the development of the parasites and to limit their pathological effects, the most prominent of which is anaemia. A major constraint on selection for trypanotolerance in cattle, for both within-breed and cross-breeding programmes, has been the absence of practical reliable markers of resistance or susceptibility. Distinct humoral immune response to trypanosome infection is the major feature of bovine trypanotolerance. The role that these responses play in the control of infection or disease is being addressed by ongoing research, but remains a matter of speculation at present. Results in recent years have shown that packed cell volume (PCV) in particular and parasitaemia, the two principal indicators of trypanotolerance, are strongly correlated to animal performance. However, although direct effects of trypanosome infections on PCV and growth are obvious, more sensitive diagnostic methods for reflecting parasite control are required so that individual animals can be categorised reliably for their parasite control capability. One key finding is the major contribution made by each of the indicators evaluated to the overall trypanotolerance variance. Preliminary genetic parameters for PCV provide evidence that trypanotolerance is not only a breed characteristic but is also a heritable trait within the N'Dama population; this brings new opportunities for improved productivity through selection for trypanotolerance. More reliable estimation of genetic parameters of the indicators may well show that these parameters must be handled simultaneously for optimal progress. This would require diagnostics for assessing parasite control capability that identify trypanosome species more accurately, especially in mixed infections. A major advantage of trypanotolerant livestock, particularly N'Dama cattle, is the resistance or adaptation of this breed to many of the important pathogenes which prevail in the sub-humid and humid tropics. Research on practical indicators of resistance to these conditions will be required to establish relevant integrated strategies based on disease-resistant livestock. Selective breeding will require the integration of the traits that farmers hold important for their production systems.

Trypanosomiasis and trypanotolerance in cattle: a role for congopain?

A Trypanosoma congolense cysteine protease (congopain) elicits a high IgG response in trypanotolerant but not in trypanosusceptible cattle during primary infections. As discussed here by Edith Authié, this observation suggests that congopain, like other parasite cysteine proteases, may play a role in pathogenicity and that more efficient immune responses to congopain may contribute to trypanotolerance.

Trypanotolerance in cattle and prospects for the control of trypanosomiasis by selective breeding

Tsetse-transmitted trypanosomiasis is one of the major constraints on the expansion of the livestock and agricultural industries in Africa. The disease affects animals and man, with direct and indirect losses estimated in billions of dollars annually. Because of the phenomenon of antigenic variation, no vaccine is available. Current prophylactic efforts must rely on tsetse control by the use of insecticides and on trypanocidal drugs. However, recent advances in our knowledge of tsetse and trypanosome biology are offering hope for alternative methods of trapping tsetse, new drugs and even vaccination. Possibly of even greater significance is the increasing sense that Africa herself might be able to contribute to the resolution of this problem. Over a period of several thousand years, she has generated cattle, such as the taurine N'Dama and West African Shorthorn breeds of West and Central Africa, that are now known to possess a significant degree of innate resistance to trypanosomiasis and several other important infectious diseases. These cattle are extremely well adapted to the environment and are now recognised as having considerable production potential. The ability to resist the development of anaemia in the face of infection, as assessed by packed red cell volume percent (PCV), has been shown to be correlated with the capacity to be productive, thereby identifying regulation of PCV as a key trait of trypanotolerance. Thus, an estimate of the ability of an infected animal to maintain PCV, following either experimental or field infection, could be used as a method for identifying trypanotolerant individuals. This could provide a means of estimating trypanotolerance heritability, thereby permitting rational breeding programmes to be instituted. Africa may thus provide the answer.

The susceptibility of strains of mice to infection with Trypanosoma congolense

The survival times of a number of strains of mice after infection with a stabilate of Trypanosoma brucei or of T congolense were examined. The mean survival times of all the strains when infected with T brucei TREU 667 ranged from 27 to 63 days. Greater disparity was observed after infection with T congolense GVR1 where the mean survival time ranged from seven (BALB/c) to 74 days (C57 Bl). It is suggested that the C57 Bl mouse might provide a laboratory model for the study of trypanotolerance in cattle.