The role of disease risk and life history in the immune function of larks in different environments

The extent to which organisms can protect themselves from disease depends on both the immune defences they maintain and the pathogens they face. At the same time, immune systems are shaped by the antigens they encounter, both over ecological and evolutionary time. Ecological immunologists often recognise these interactions, yet ecological immunology currently lacks major efforts to characterise the environmental, host-independent, antigenic pressures to which all animals are exposed. Failure to quantify relevant diseases and pathogens in studies of ecological immunology leads to contradictory hypotheses. In contrast, including measures of environmental and host-derived commensals, pathogens and other immune-relevant organisms will strengthen the field of ecological immunology. In this paper we examine how pathogens and other organisms shape immune defences and highlight why such information is essential for a better understanding of the causes of variation in immune defences. We introduce the concept of ‘operative protection’ for understanding the role of immunologically-relevant organisms in shaping immune defence profiles, and demonstrate how the evolutionary implications of immune function are best understood in the context of the pressures that diseases and pathogens bring to bear on their hosts. We illustrate common mistakes in characterising these immune-selective pressures, and provide suggestions for the use of molecular and other methods for measuring immune-relevant organisms. Nicholas P.C. Horrocks, Kevin D. Matson and B. Irene Tieleman Integrative and Comparative Biology 51: 563-576 (2011) Integrating immunology and ecology The immune system bridges the divide between internal and external environments, integrating an organism’s physiology and environment. In doing so, the immune system acts as a barrier to infection and disease, identifying threats and coordinating necessary responses. Despite its complexity, immunologists have elucidated many of the cellular processes and specific mechanisms that allow the immune system to function. Yet our knowledge of how evolutionary pressures shape immune systems is still incomplete. Ecological immunology promotes the use of immunological measures to test ecological and evolutionary hypotheses. The field arose from a desire to explain the variation in immune function that is observed within and among individuals, populations and species, across environments and over time. Many factors influence, and can generate variation in, immune responses: these include sex, nutritional status, social dominance, exercise, and seasonality, as well as trade-offs in resource allocation between the immune system and other physiological systems such as reproduction (Sadd and Schmid-Hempel 2009; Schulenburg et al. 2009). Over both ecological and evolutionary timescales however, the most enduring selective pressures on the immune system are the myriad challenges posed by everything that immune systems encounter. Particularly important in terms of evolution are interactions between the immune system and organisms with the ability to live in, or on, a host and the potential to evolve in response to current immune defences. We refer to the specific suite of components that generate these evolutionary and ecological selective forces on the immune system as the ‘immunobiome’ and their ability to shape immune defences as ‘immunobiotic pressure’ (Fig. 2.1). Understanding the interactions of the immune system with immunobiomes is essential for helping to explain patterns of immunological variation. In light of immunological costs, animals should match their immune defences* to the threats that they face (Sheldon and Verhulst 1996; Tschirren and Richner 2006). However, the nature of immunobiomes is poorly understood. For example, does their basic composition differ among environments? Which components most strongly shape immune defences in which hosts? Understanding these issues will be central to solving broader challenges in immunology such as the consequences of emergent infectious diseases (Jones et al. 2008) or the consequences for health of altering commensal microbial communities (Blaser and Falkow 2009). We propose that to advance ecological immunology, measures of the immunobiome that are independent of immune indices should be developed 18 C H A P T E R 2 * Any anatomical, chemical, physiological or behavioural barrier maintained by an animal that inhibits or controls the establishment and reproduction of any element of the immunobiome within or on the animal. and incorporated into future studies. Much as data on availability of food are required for an understanding of diet selection (e.g. Belovsky 1981) and environmental temperature profiles are required for explaining heat balance (e.g. Tieleman and Williams 2002), knowledge of immunobiomes and immune stimuli is essential when testing hypotheses in ecological immunology. Rather than being relegated to anonymous, yet highly relevant sources of variation, the diverse constituents of the immunobiome and the evolutionary pressures they exert must be seen as central to ecoimmunological studies (Bordes and Morand 2009; Sadd and Schmid-Hempel 2009; Graham et al. 2011; Pedersen and Babayan 2011). Interactions with entire immunobiomes shape immune defences, but pathogens and commensals are particularly important Animals live in diverse and variable environments and their immune systems must interact with and respond to equally diverse and variable immunobiomes. However, across immunobiomes, two categories of organisms that lie at all points 19 P A T H O G E N P R E S S U R E A N D I M M U N E D E F E N C E 'Immunobiome' Pathogens Commensals Antigenic universe Figure 2.1. A representation of the antigenic universe, which consists of all the possible antigens that any immune system could ever encounter. This universe includes antigenic, immunogenic, inflammatory and toxic agents. Within the antigenic universe is the immunobiome. The immunobiome contains all the living organisms that can live in or on a host and with the potential to evolve in response to immune defences. The immunobiome does not include other immuno-reactive particles such as dust that cannot multiply. Two major components of the immunobiome, in terms of the evolution of the immune system, are commensals and pathogens. Since some commensals may be pathogenic under suitable conditions, these groups are not mutually exclusive. Immunobiome components that fall outside these two categories (light grey area) include environmental microbes such as ‘pseudo-commensals’ (Rook 2009), which although regularly encountered by hosts, do not gain any benefit from their temporary association with a host, yet may still shape regulatory circuits of the immune system. Scaling of the different subsets is arbitrary. along a continuum from benign, or even beneficial, to harmful, are expected to be particularly important sources of immunobiotic pressure (Fig. 2.1). At the detrimental end of this continuum are pathogens. These microparasites (viruses, bacteria, fungi and protists) and macroparasites (e.g. helminths, ticks, lice) can potentially harm host tissues through their inherent ability to breach immune defences that normally restrict other organisms. Pathogens seek to circumvent host immune defences and may disrupt normal immune processes (Tortorella et al. 2000; Finlay and McFadden 2006). This might include immunosuppression (Babu et al. 2006; Jackson et al. 2009) or shifting of the immune system towards a specific mix of defences (Maizels and Yazdanbakhsh 2003). Of equal importance to the evolution of the immune system, commensals normally sit at the benign end of the pathogenicity spectrum. Benefiting from intimate associations with their host, commensals can also modulate immune responses and play an essential role in development of the immune system (Rakoff-Nahoum et al. 2004; Mazmanian et al. 2005; Rook 2009; Round and Mazmanian 2009). Different commensal communities might offer distinct advantages or disadvantages in terms of immunomodulation (Jackson et al. 2009) and colonization by pathogens (Stecher and Hardt 2008; Stecher et al. 2010). Under some circumstances, organisms that normally behave commensally can become pathogenic (sensu ‘amphibiosis’; Rosebury 1962). Commensals that escape immune controls by inappropriately breaching defensive barriers (e.g. the intestinal epithelium) may also become de facto pathogens (Blaser and Falkow 2009). Overall, interactions with the entire immunobiome, encompassing organisms associated with the full range of the pathogenicity spectrum, shape both immune defences and immunobiotic components themselves, and can have implications for health and survival (Round and Mazmanian 2009). Hosts might encounter immunobiomes that vary temporally (e.g. at different times of the day, or across seasons) or spatially (e.g. small scale differences in use of habitat, or large-scale differences in biogeography). At ecological scales immunobiotic pressures mould individual responses and physiological condition. Immune function interacts with and is influenced by each antigen (pathogenic, commensal or otherwise) encountered over the lifetime of an individual, from in utero or in ovo (Boulinier and Staszewski 2008; Grindstaff 2008) to adulthood. Nonetheless, these relationships are ultimately governed by an immune system that has been shaped through evolution. At evolutionary scales, differences in composition and function of immunobiomes and levels of exposure to them are expected to lead to genetically-based changes in the organization of the immune system, with immunobiotic pressures shaping immuno-defensive architecture.