Genetic Resistance to Experimental Infection with Mycobacterium bovis in Red Deer ( Cervus elaphus )

Abstract

Tuberculosis (Tb) caused by Mycobacterium bovis is a worldwide threat to livestock and humans. One control strategy is to breed livestock that are more resistant to Mycobacterium bovis. In a 3-year heritability study 6 farmed red deer stags were selected from 39 on the basis of their differing responses to experimental challenge via the tonsillar sac with approximately 500 CFU of M. bovis. Two stags remained uninfected, two were moderately affected, and two developed serious spreading Tb. Seventy offspring, bred from these six stags by artificial insemination using stored semen, were similarly challenged with M. bovis. The offspring showed patterns of response to M. bovis challenge similar to those of their sires, providing evidence for a strong genetic basis to resistance to Tb, with an estimated heritability of 0.48 (standard error, 0.096; P < 0.01). This is the first time the heritability of Tb resistance in domestic livestock has been measured. The breeding of selection lines of resistant and susceptible deer will provide an ideal model to study the mechanisms of Tb resistance in a ruminant and could provide an additional strategy for reducing the number and severity of outbreaks of Tb in farmed deer herds. Laboratory studies to identify genetic and immunological markers for resistance to Tb are under way. Preliminary studies showed no associations between NRAMP or DRB genes and resistance to Tb in deer. Patterns of immune responses seen in resistant animals suggest that both innate and acquired pathways of immunity are necessary to produce the resistant phenotype.Tuberculosis (Tb) is one of the most widespread diseases of mankind and animals. Although the majority of cases of human Tb are caused by Mycobacterium tuberculosis, a small proportion are caused by Mycobacterium bovis carried by cattle and other domestic animals (25). In order to reduce this zoonotic risk, most developed countries have attempted to eradicate bovine Tb from their domestic animals. The problem is compounded by the establishment of Tb in wildlife reservoirs such as badgers in the United Kingdom (31) and Ireland (8,23), buffalo and antelope in South Africa (25), and bison and deer in North America (25). In New Zealand, traditional "testand-slaughter" control methods (24) and the killing of wildlife vectors, such as opossums (Trichosurus vulpecula) and ferrets (Mustela furo), have nearly halved the prevalence of Tb on farms in the last 5 years. The percentage of infected herds was 1.5% of the 60,000 cattle herds and 2.3% of the 5,200 deer herds recorded at the end of June 1998 (2). However, to reach the internationally accepted level of 0.2% herd infection rate, additional strategies are needed. One strategy for reducing the incidence of Tb in domestic livestock, which has not been used previously, is to select for increased genetic resistance.Red deer have been farmed in New Zealand for more than 25 years, and they currently number over 1.7 million on approximately 5,200 farms. At the end of June 1998 there were 118 known infected her...

Experimental challenge models for Johne's disease: A review and proposed international guidelines

“…Variable breed or strain resistance to mycobacterial infection has been well described in mice (see Section 7.1, murine models). Genetic resistance has also been described in cattle (Koets et al, 2000;Mortensen et al, 2004) and red deer (Mackintosh et al, 2000), but not in goats and sheep. Breed or strain of animal should be specified in the event that an associated resistance might exist.…”

“…High levels of heritable resistance and susceptibility to mycobacterial infection are documented in deer (Mackintosh et al, 2000). Deer appear to be a useful host for disclosing diagnostic markers by which to monitor infection , protective immunity, or resistance to infection.…”

Diagnóstico imuno-histopatológico da paratuberculose subclínica em bovinos no estado do Rio de Janeiro

“…Estes animais tinham entre 4 e 10 anos de idade, no entanto, não foi possível estimar o período de incubação, a quantidade de Map ingerida, se estes animais se infectaram quando jovens ou na idade adulta, ou ainda, se eram resistentes ao desenvolvimento de lesões acentuadas. Pesquisadores têm observado a resistência/susceptibilidade genéti-ca à tuberculose e paratuberculose em várias espécies de ruminantes , Korou et al 2010, Osterstock et al 2010, Reddacliff et al 2005, Mackintosh et al 2000. Tais parâmetros poderiam auxiliar no delineamento de estratégias de controle em rebanhos infectados, a fim de minimizar as possibilidades de ingestão de Map, selecionar indivíduos resistentes à infecção pelo agente, ou ainda, estabelecer manejo diferenciado na propriedade.…”

Immunocontraception of mammalian wildlife: ecological and immunogenetic issues

“…The existence of genes governing response to pathogens is well documented in humans for malaria (Hill 2001), tuberculosis (Blackwell 1998, Bellamy 2003), and HIV (McNicholl & Cuenco 1999, Carrington & O'Brien 2003. Relevant examples are found in New Zealand Red Deer in which susceptibility to tuberculosis has high heritability (Mackintosh et al 2000) and in the NRAMP1 association with the human response to leishmaniasis (Bucheton et al 2003). The complexities of the co-evolution of pathogens and hosts and its biomedical significance are beginning to be unraveled (Woolhouse et al 2002).…”