Should we aim for genetic improvement in host resistance or tolerance to infectious pathogens?

There is an imperative to consider alternative strategies to pharmaceuticals to control infectious diseases amongst livestock. Recent advances in genetics and genomics have highlighted the potential for genetic control strategies to maintain high health and performance levels in livestock populations. This special research topic focuses on two alternative host defence strategies for coping with infectious pathogens that could be tackled for genetic improvement: host resistance vs. host tolerance. Resistance refers to mechanisms that restrict the reproduction rate of pathogens within a host, e.g., by blocking pathogen entry or limiting pathogen replication. Tolerance, in contrast, refers to the ability of a host to limit the detrimental impact pathogens can inflict on host performance (e.g., growth, milk/egg production, and fertility), without affecting pathogen burden per se. Tolerance captures all immune mechanisms that are not directly related to the reduction of pathogen burden, such as damage prevention or repair, as well as mechanisms that regulate self-harm inflicted by immune response components. In contrast to the rapid expansion of identified genetic loci associated with host resistance, information of genetic loci or pathways associated with tolerance mechanisms is extremely sparse. However, a deeper understanding of the genetic control underlying both mechanisms is important in order to decide upon disease control strategies and avoid undesirable outcomes of genetic improvement programmes. This is firstly because at genetic level, resistance and tolerance may be antagonistically related. Secondly, although resistance and tolerance may have a similar impact on individual health and performance, they can have contrasting effects on performance outcomes and on disease prevalence at a population level. In particular, whilst improving host resistance could lead to disease eradication, this is unlikely if hosts are tolerant, as they can harbor the pathogen without showing obvious symptoms. On the other hand, it has been argued that increasing host resistance (but not tolerance) would fuel the arms race between host and pathogen, and stimulate pathogen evolution toward higher virulence. Furthermore, whereas disease resistance mechanisms are often pathogen-specific (e.g., mobilization of specific immune cells), tolerance mechanisms that prevent or repair damage may be more host than pathogen specific, and may thus offer generic protection for a range of pathogens. Hence, changing tolerance may be more beneficial in situations where individuals are exposed to a variety of pathogens or pathogen strains (as is the case in many commercial farms), with high risk of pathogen evolution, and where disease eradication has proven difficult (e.g., if asymptomatic carriers are present). In contrast to evolutionary biology and plant breeding, livestock breeding has only recently started to appreciate the importance of distinguishing between resistance and tolerance to pathogens and to study their relationship and implications. This special research topic draws together animal scientists with expertise in molecular and quantitative genetics, immunology, epidemiology, evolutionary biology, and mathematical modeling to address the question “Should we aim for genetic improvement of host resistance or host tolerance to infectious pathogens” from different perspectives. The diverse contributions to this topic: