Disease Tolerance as a Defense Strategy

Abstract

The immune system protects from infections primarily by detecting and eliminating the invading pathogens; however, the host organism can also protect itself from infectious diseases by reducing the negative impact of infections on host fitness. This ability to tolerate a pathogen’s presence is a distinct host defense strategy, which has been largely overlooked in animal and human studies. Introduction of the notion of “disease tolerance” into the conceptual toolkit of immunology will expand our understanding of infectious diseases and host pathogen interactions. Analysis of disease tolerance mechanisms should provide new approaches for the treatment of infections and other diseases.

Disease tolerance and immunity in host protection against infection

“…This is coupled to the induction of cellular and tissue regenerative responses that restore the functional output of damaged parenchyma tissues 3,23 . As discussed in further detail below, different types of infection impose distinct forms of stress and damage to host parenchyma cells, suggesting that tissue damage control mechanisms 3 might act in a somewhat pathogen class-specific manner that reflects these differences such as to effectively establish disease tolerance against diverse types of infection 6 . While there are clearly parallels between the protective effect exerted by tissue damage control mechanisms in the context of infectious and non-infectious diseases 1, 6, 24 , we shall restrict our discussion here to infectious diseases.…”

“…However, the trade-off of this resistance mechanism can be particularly high, depending on the relative capacity of different tissues to withstand cell loss without compromising tissue function and homeostasis 6 . The pathophysiological relevance of this defense strategy is supported by the number of mechanisms deployed by intracellular pathogens to promote or inhibit host genetic programs controlling programmed cell death, presumably as a strategy to escape resistance to infection 70 .…”

“…This evolutionarily conserved host defense strategy, which was first described in plants 7,8 , is fully operational in flies 9,10 and mammals, including rodents 11,12 and humans 13 , where it preserves host homeostasis in response to viral 14,15 , bacterial [15][16][17][18] , fungal 19 and protozoan 11,13,20,21 infections. In contrast to resistance to infection, disease tolerance does not exert a direct negative effect on these pathogens 6 .…”

Integrating nutrition and immunology: A new frontier

“…Disease tolerance is a defense strategy that reduces the negative impacts of the infection on host fitness without reducing the parasite load. The term employed here is different to immunological tolerance (i.e., the process by which the immune system fails to attack an antigen), but rather captures the idea that the costs of the infection can be reduced through reducing the damage caused by the infection and activation of the immune system on host tissues (Ayres and Schneider, 2012;Medzhitov et al, 2012). For example, Ayres and Schneider, (2009) found that during Salmonella infections, food-restricted Drosophila and flies mutant for the gustatory receptor, gr28b, had similar levels of bacteria to wild-type individuals but they lived longer.…”

The burden of extended-spectrum β-lactamase-producing Enterobacteriaceae in patients with cirrhosis

“…Alternatively the dissemination of infection may result in tissue damage because bacteria express virulence factors with deleterious cell effects (e.g., alterations in homeostasis of endoplasmic reticulum or mitochondria; impairment of the induction of tissue repair program) [21]. Future studies should address these points.…”