- Email: [email protected]
Immunity and immunogenetics—newapproaches to controlling worm infections in sheep
Br. vet.J. (1995). 151,111
GUEST EDITORIAL IMMUNITY AND IMMUNOGENETICS~ NEW APPROACHES TO CONTROI,I,ING WORM INFECTIONS IN SHEEP
Control of i'nfections with gastrointestinal (GI) nematodes in sheep is a perennial and increasingly difficult problem. The biology of these worms and the nature of their transmission--ingestion of infective larvae as animals graze on contaminated pasture--means that there is a severe risk of heavy infection when stocking rates are high and where climatic conditions favour larval survival. Scouring in lambs, loss of condition, loss of weight and poor breeding are common consequences of infection; the most serious pathogens, such as the blood-sucking H a e m o n c h u s contortus, can cause severe anaemia and kill. At present, control of GI worms relies on pasture management and, more heavily, on chemotherapy, but drug resistance has become a significant concern, several species now showing multiple resistance to many of the common anthelmintics. Atten.tion is once again turning to the possibility of immune control and two options are being explored: development of vaccines; and improvement of stock by selective breeding for greater immunity to infection. Prospects for effective vaccines against some GI nematodes now seem brighter, but many practical problems remain. The option of selective breeding is being pursued in several countries, most actively in Australia and New Zealand. The importance of this approach is reflected in the many publications available, two of which give useful reviews (Gray & Woolaston, 1991; Owen & Axford, 1991). Breeding animals for improved resistance to parasitic infection rests on three assumptions: (1) infected animals develop immune responses and these can control parasites; (2) immune responses are genetically determined and variable between individ• u a l s a n d breeds; (3) the genetic trait 'increased resistance' is heritable and can be selected. Each of these assumptions is supported by experimental studies with laboratory infections in rodents (Wakelin & Blackwell, 1988) and it is clear that they are valid also for domestic stock. Individual and breed variation in resistance to GI nematode infections in sheep has been known to veterinary scientists for many years and to shepherds for much longer. The evidence that resistance depends upon acquired immune responses as well as physiological resilience (the ability to withstand the consequences of 0007-1935/95/020111-03/$08.00/0
© 1995 Bailli~reTindall
112
BRITISH VETERINARY.JOURNAL,
151, 2
infection) is more recent, but is unequivocal. That such immune responses are under direct genetic control is also now established, although the detail of this control is less well understood than in humans or mice. The possibility of selective breeding to improve flock resistance was mooted nearly 60 years ago (Gregory, 1937) and has been achieved experimentally without the significant loss of productivity that was feared. Larger scale development of the approach is dependent, however, on the identification of easily detected markers for resistance that can be used to select breeding stocks and monitor their performance. The review by Hohenhaus and Outteridge in this issue of the Journal provides a comprehensive and critical summary of our present knowledge of such markers, all of which can be considered as direct or indirect correlates of the responses thought to be relevant to functional immunity against GI worms, and many of which have been the focus of work by the senior author. Immunity against GI nematodes is T cell-dependent, involves intestinal inflammatory changes and is facilitated by specific anti-parasite antibodies. A consensus view is that immunity is multifactorial and that the contribution of individual components may vary without necessarily interfering with the overall effectiveness of resistance. This being so, it is unlikely that any one marker can be an absolute predictor of resistance. A variety of markers may be useful and these will reflect the processes of antigen presentation and T lymphocyte function [major histocompatibility complex (MHC) markers, T cell proliferation], inflammatory response potential (eosinophilia) and serological response (levels of specific antibodies). Progress has been made with each of these; the evidence of this progress and a realistic evaluation of the value of the markers so far studied are clearly brought out in the review. In terms of MHC markers, although most progress has so far come from serological detection of allotypes, it is clear that future progress will depend more heavily on the use of molecular probes. Such probes will have even more value if they can be used to detect the non-MHC (background) genetic influences that play such an important role in determining the inflammatory and antibody-based components of resistance. Compared with the time, money and resources that have gone into selective breeding for production characteristics over many years, the science of selection for parasite resistance is in its infancy and is under-resourced. As Hohenhaus and Outteridge make clear, however, real progress is being made and the potential rewards in terms of improved animal husbandry are likely to be very significant. D. WAKELIN
Department of Life Science, University of Nottingham, Nottingham NG7 2RD, UK
REFERENCES
G~av, G. D. & WOOLASTON,R. R. (eds.) (1991). Breedingfor Disease Resistance in Sheep. Melbourne: Wool Research and Development Corporation. HOHENHAUS,M. A. & OUTrERID(;E,P. M. (1995). The ilnmunogenetics of resistance to 75"icho-
IMMUNITY AND IMMUNOGENETICS
113
strongyh,s cohdn'iformis and Haemonchus contortus parasites in sheep. Br~tish Veterinary Jou~,a1151, 119-140. OWEN,J. B. & AXVORt),R. F. E. (eds.) (1991). Breeding for Disease Resistance in Farm Animals. Wallingford, Oxon: C.A.B. International. G~E~,ORV, P. W. (1937). The possibility of establishing within breeds lines of sheep that are genetically resistant to stomach worms. Proceedings of the American Society for Animal Production pp. 316-324. W..t~:tJN, D. & Bb~CKWELL,J. M. (eds.) (1988). Genetics of Resistance to Bacterial and Parasitic Infection. London: Taylor and Francis.
GUEST EDITORIAL IMMUNITY AND IMMUNOGENETICS~ NEW APPROACHES TO CONTROI,I,ING WORM INFECTIONS IN SHEEP
Control of i'nfections with gastrointestinal (GI) nematodes in sheep is a perennial and increasingly difficult problem. The biology of these worms and the nature of their transmission--ingestion of infective larvae as animals graze on contaminated pasture--means that there is a severe risk of heavy infection when stocking rates are high and where climatic conditions favour larval survival. Scouring in lambs, loss of condition, loss of weight and poor breeding are common consequences of infection; the most serious pathogens, such as the blood-sucking H a e m o n c h u s contortus, can cause severe anaemia and kill. At present, control of GI worms relies on pasture management and, more heavily, on chemotherapy, but drug resistance has become a significant concern, several species now showing multiple resistance to many of the common anthelmintics. Atten.tion is once again turning to the possibility of immune control and two options are being explored: development of vaccines; and improvement of stock by selective breeding for greater immunity to infection. Prospects for effective vaccines against some GI nematodes now seem brighter, but many practical problems remain. The option of selective breeding is being pursued in several countries, most actively in Australia and New Zealand. The importance of this approach is reflected in the many publications available, two of which give useful reviews (Gray & Woolaston, 1991; Owen & Axford, 1991). Breeding animals for improved resistance to parasitic infection rests on three assumptions: (1) infected animals develop immune responses and these can control parasites; (2) immune responses are genetically determined and variable between individ• u a l s a n d breeds; (3) the genetic trait 'increased resistance' is heritable and can be selected. Each of these assumptions is supported by experimental studies with laboratory infections in rodents (Wakelin & Blackwell, 1988) and it is clear that they are valid also for domestic stock. Individual and breed variation in resistance to GI nematode infections in sheep has been known to veterinary scientists for many years and to shepherds for much longer. The evidence that resistance depends upon acquired immune responses as well as physiological resilience (the ability to withstand the consequences of 0007-1935/95/020111-03/$08.00/0
© 1995 Bailli~reTindall
112
BRITISH VETERINARY.JOURNAL,
151, 2
infection) is more recent, but is unequivocal. That such immune responses are under direct genetic control is also now established, although the detail of this control is less well understood than in humans or mice. The possibility of selective breeding to improve flock resistance was mooted nearly 60 years ago (Gregory, 1937) and has been achieved experimentally without the significant loss of productivity that was feared. Larger scale development of the approach is dependent, however, on the identification of easily detected markers for resistance that can be used to select breeding stocks and monitor their performance. The review by Hohenhaus and Outteridge in this issue of the Journal provides a comprehensive and critical summary of our present knowledge of such markers, all of which can be considered as direct or indirect correlates of the responses thought to be relevant to functional immunity against GI worms, and many of which have been the focus of work by the senior author. Immunity against GI nematodes is T cell-dependent, involves intestinal inflammatory changes and is facilitated by specific anti-parasite antibodies. A consensus view is that immunity is multifactorial and that the contribution of individual components may vary without necessarily interfering with the overall effectiveness of resistance. This being so, it is unlikely that any one marker can be an absolute predictor of resistance. A variety of markers may be useful and these will reflect the processes of antigen presentation and T lymphocyte function [major histocompatibility complex (MHC) markers, T cell proliferation], inflammatory response potential (eosinophilia) and serological response (levels of specific antibodies). Progress has been made with each of these; the evidence of this progress and a realistic evaluation of the value of the markers so far studied are clearly brought out in the review. In terms of MHC markers, although most progress has so far come from serological detection of allotypes, it is clear that future progress will depend more heavily on the use of molecular probes. Such probes will have even more value if they can be used to detect the non-MHC (background) genetic influences that play such an important role in determining the inflammatory and antibody-based components of resistance. Compared with the time, money and resources that have gone into selective breeding for production characteristics over many years, the science of selection for parasite resistance is in its infancy and is under-resourced. As Hohenhaus and Outteridge make clear, however, real progress is being made and the potential rewards in terms of improved animal husbandry are likely to be very significant. D. WAKELIN
Department of Life Science, University of Nottingham, Nottingham NG7 2RD, UK
REFERENCES
G~av, G. D. & WOOLASTON,R. R. (eds.) (1991). Breedingfor Disease Resistance in Sheep. Melbourne: Wool Research and Development Corporation. HOHENHAUS,M. A. & OUTrERID(;E,P. M. (1995). The ilnmunogenetics of resistance to 75"icho-
IMMUNITY AND IMMUNOGENETICS
113
strongyh,s cohdn'iformis and Haemonchus contortus parasites in sheep. Br~tish Veterinary Jou~,a1151, 119-140. OWEN,J. B. & AXVORt),R. F. E. (eds.) (1991). Breeding for Disease Resistance in Farm Animals. Wallingford, Oxon: C.A.B. International. G~E~,ORV, P. W. (1937). The possibility of establishing within breeds lines of sheep that are genetically resistant to stomach worms. Proceedings of the American Society for Animal Production pp. 316-324. W..t~:tJN, D. & Bb~CKWELL,J. M. (eds.) (1988). Genetics of Resistance to Bacterial and Parasitic Infection. London: Taylor and Francis.