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Proc Biol Sci. Feb 22, 2008; 275(1633): 353–361.
Published online Dec 5, 2007. doi:  10.1098/rspb.2007.1211
PMCID: PMC2213712

Symbiont-mediated protection

Abstract

Despite the fact that all vertically transmitted symbionts sequester resources from their hosts and are therefore costly to maintain, there is an extraordinary diversity of them in invertebrates. Some spread through host populations by providing their hosts with fitness benefits or by manipulating host sex ratio, but some do not: their maintenance in host lineages remains an enigma. In this review, I explore the evolutionary ecology of vertically transmitted symbionts and their impact on host resistance, and provide an overview of the evidence for the three-way interactions between these symbionts, natural enemies and invertebrate hosts. A number of recent empirical and theoretical studies suggest that vertically transmitted symbionts may protect their hosts from pathogens. If this ‘symbiont-mediated protection’ is widespread, it is likely that vertically transmitted symbionts contribute significantly to variation in measures of invertebrate resistance to natural enemies.

Keywords: symbiont, vertical transmission, resistance, evolutionary ecology, invertebrate immunity, protection

1. Introduction

Symbiosis describes a close relationship between members of different species, such as the associations between large multicellular organisms and microbes. The microbial partners are called symbionts (reviewed by Moran 2006). When the interaction benefits both partners, it is a mutualistic symbiosis, but when the symbiont benefits at the expense of its host, the association is one of parasitic symbiosis. The potential durable interactions between hosts and symbionts may lie anywhere on a continuum between parasitism and mutualism (Combes 2001). Generally speaking, microbes at the parasitic end of the symbiosis continuum tend to transmit horizontally (horizontal transmission, HT) from one host to another, while those at the mutualistic end of the symbiosis continuum tend to transmit vertically (vertical transmission, VT) from parent to offspring.

Invertebrates possess an extraordinary diversity of VT symbionts (e.g. Wolbachia, Rickettsia, Spiroplasma, Arsenophonus, Flavobacteria, Bacteroidetes and microsporidia Yen & Barr 1971; Werren et al. 1995; Hurst et al. 1999; Stouthamer et al. 1999; Dunn & Smith 2001; Schulenburg et al. 2001; Weeks et al. 2001, 2003; Tsuchida et al. 2002; Hunter et al. 2003; Zchori-Fein & Perlman 2004; Perlman et al. 2006), which can broadly be categorized into two groups based on their biology and evolutionary history (summarized by Dale & Moran (2006)). First, there are primary symbionts that are obligate for host survival and reproduction, are strictly vertically transmitted and have been associated with their host lineages for a long evolutionary time. An example is Buchnera aphidicola, a Gammaproteobacteria that provides essential nutrients to aphids (Buchner 1965). Second, there are secondary symbionts that are facultative and can undergo low levels of HT by which they can colonize new hosts. However, as they are predominantly vertically transmitted, in order to spread and persist in host populations they often confer some fitness advantage to infected over uninfected individuals, for example, by increasing host survival or reproductive output. An example of a secondary symbiont is the Gammaproteobacteria Arsenophonus (e.g. Dale et al. 2006). Other secondary symbionts spread because they manipulate host reproduction to increase their transmission through the maternal line; these are the reproductive parasites, such as Wolbachia pipientis (Hurst et al. 2005), which can spread even if it is deleterious to host fitness. Wolbachia is generally not necessary for host survival, but in some hosts it is an obligate symbiont: for example, a strain infecting the Drosophila parasitoid, Asobara tabida is necessary for host oogenesis (Dedeine et al. 2001). The impact of secondary symbionts on host fitness might depend on the environment such that they might be beneficial in one environment and deleterious in another. This is likely to determine why some populations are fixed for secondary symbiont infections while others are not (e.g. Montllor et al. 2002).

Infections by VT symbionts are often asymptomatic—they have very few pathogenic effects on their hosts—and as a result they are often undetected unless specifically screened for by molecular methods. The diversity and presence of VT symbionts require an explanation since they exploit their host for resources and are therefore likely to be costly to maintain. In some cases, their persistence can be explained because they undergo low levels of HT, but in general symbionts that are strictly vertically transmitted must either increase the fitness of their host or manipulate host reproduction in ways that benefit their own transmission in order to be maintained in host populations (Werren & O'Neill 1997; Hurst et al. 2005). However, there are examples where symbionts do not interfere with host reproduction, provide no direct fitness benefit to their host and the mechanism underpinning their maintenance is not understood (e.g. Hoffmann et al. 1996).

To complicate matters further, an additional conflict arises when HT parasites (HTPs) and VT symbionts find themselves infecting the same host, since the former reduce host fecundity and often kill the host, while the latter's fitness is intrinsically linked to that of its host owing to its transmission mode (Rigaud & Haine 2005), and it requires that the host survives to reproduce—I propose that the conflict between VT symbionts and HTPs is resolved when VT symbionts provide their host with resistance to pathogens and parasites. The term ‘symbiont-mediated resistance’ was first coined by Oliver et al. (2005) in relation to the empirical evidence that secondary symbionts confer protection against parasitoid attack to their aphid hosts. Such phenomena have been described as ‘interference’ in theoretical studies (Jones et al. 2007) and have been suggested to be an overlooked component of invertebrate immune defence (Loker et al. 2004). The consequence of this line of reasoning is that any direct fitness effects of VT symbionts on their hosts (that explain their maintenance) may therefore be realized (and so observed) only when symbiont-bearing hosts are superinfected by horizontally transmitted pathogens.

In this review, I summarize the theoretical studies that have examined the interactions between VT symbionts and HTPs. I then present empirical evidence for symbiont protection of their hosts from natural enemies, discuss the mechanisms by which they do this and consider the interactions between VT symbionts and host immune defences. While this review just deals with invertebrate symbionts, symbiont-mediated protection is also relevant to vertebrates: a recent study found that mice infected by latent herpesviruses are resistant to infection by the bacterial pathogens Listeria monocytogenes and Yersinia pestis (Barton et al. 2007).

2. Theoretical considerations on interference between VT symbionts and pathogens

In order to be maintained in a host population, the probability of a VT symbiont being successfully transmitted to the next generation must be greater than 1 (Lipsitch et al. 1995; Lively et al. 2005). This may be achieved if the VT symbiont increases host fitness (e.g. by increasing host fecundity and/or decreasing host mortality). It may also be greater than 1 if it can also transmit horizontally (Lipsitch et al. 1995) and, in some cases, a VT symbiont can increase in frequency in a host population even if it reduces host fitness because the symbiont manipulates host reproduction to gain increased transmission (Werren & O'Neill 1997). The dynamics of a host population containing a VT symbiont are complicated when the host population is also infected by an HTP because an HTP will increase the host population death rate, and eventually reduce population density (Lively et al. 2005). Lipsitch et al. (1996) examined competition between two parasite strains where both parasites can transmit vertically and horizontally. In most cases, VT symbionts are predominantly vertically transmitted, but Lipsitch et al. (1996) also considered the situation in which one of the strains was strictly vertically transmitted and predicted that it could increase in a population that was infected by a HTP but it could not eliminate the HTP. More recently, four papers have specifically examined the theoretical interactions between VT symbionts and HTPs. Three of these models assume that there is complete protection, i.e. a HTP cannot infect hosts that are already infected by a VT symbiont (Lively et al. 2005; Faeth et al. 2007; Dhirasakdanon & Thieme submitted). However, the assumption that a host cannot be simultaneously infected by a VT symbiont and an HTP is not always biologically realistic because empirical studies have demonstrated that hosts can be simultaneously infected by parasites with both forms of transmission (e.g. Oliver et al. 2003, 2005; Haine et al. 2005). Owing to the nature of their transmission mode, VT symbionts will inevitably infect a host individual first, after which HTPs may superinfect the same hosts (e.g. Oliver et al. 2003, 2005; Haine et al. 2005). In their model, Jones et al. (2007; box 1) allow the HTP to superinfect hosts that are already infected by a VT symbiont.

Box 1. Protection by vertically transmitted symbionts

A vertically transmitted parasite (VTP) infection can affect the population dynamics of a system containing a vertically transmitted symbiont, a host and a horizontally transmitted parasite (HTP). The host can be infected with either HTP or VTP, with the HTP superinfecting the VTP-infected host. Figure 1 describes the interactions.

β is the transmission efficiency of the HTP to infect the susceptible host and δ is the amount of protection the VTP affords the host that it is infecting. Susceptible hosts are therefore susceptible to horizontal infection at rate β, and vertically infected hosts are susceptible to horizontal infection at rate (1−δ)β (dashed arrows). a is the birth rate (open arrows). The VTP has a vertical transmission efficiency of p and therefore increases in numbers by p×a, and contributes (1−p)a to the uninfected hosts (solid arrow). Increasing protection allows the VTP to persist in the host–HTP system, and also increases total host population numbers. The host population growth rate is density dependent.

Population Dynamics

Protection by the VTP leads to an increase in the HTP numbers until nearly complete protection occurs at which point there is a clear reduction in HTP numbers and an increase in the densities of both the VTP and uninfected hosts (figure 2). In a system where the HTP transmits with free-living infectious particles, the introduction of the protecting VTP stabilizes oscillating interactions, reducing amplitudes and the tendency to cycle (Jones et al. 2007).

When a VT symbiont is introduced to a population at equilibrium for a HTP, Lively et al. (2005) predicted that the VT symbiont can reduce the frequency and number of hosts infected by an HTP. It can also increase the number of hosts in the population at equilibrium relative to a population infected only by the HTP: the number of uninfected hosts increases as the VT symbiont increases in frequency, and the frequency of both uninfected and VT symbiont-infected hosts increases with the transmission probability of the VT symbiont. Although the VT symbiont can only invade an uninfected population if its transmission probability is greater than 1, which is biologically impossible in this theoretical system, it can also invade a population that is already infected by an HTP because the HTP drastically reduces host population density, and the effect of host density on individuals' birth and death rates is reduced (Lively et al. 2005). Interestingly, the model predicted that density-dependent virulence of the HTP increases as the transmission of the VT parasite increases because the total host density increases with VT parasite transmission (Lively et al. 2005). A study with similar assumptions predicted that coexistence is possible provided the VT strain causes less mortality than the HT strain (Dhirasakdanon & Thieme submitted), and Faeth et al. (2007) predicted that a VT strain, which would die out on its own, was able to persist by protecting its host against a more harmful HT strain. In all three of these studies the interesting prediction is that, even when the probability of a VT symbiont being successfully transmitted to the next generation is less than or equal to 1 (therefore preventing it from invading an uninfected population), it can invade a host population if it protects the host population from an HTP.

By contrast, both VT symbionts and HTPs can simultaneously infect the same host. Jones et al. (2007) made predictions about the population dynamics of a population in which a VT symbiont can protect its host by reducing the transmission efficiency of an HTP. In a population of susceptible hosts, hosts infected by VT symbionts and HTPs, the proportion of hosts infected by VT symbionts and HTPs increases as the protection conferred by the VT symbiont increases, until a threshold is reached at which the protection is so large that there are very few individuals infected by the VT symbiont that are becoming infected by the HTP. As protection reaches 100%, the density of hosts infected by the HTP decreases (Jones et al. 2007; box 1), and there is an overall increase in host population density (as also predicted by Lively et al. (2005), Faeth et al. (2007) and Dhirasakdanon & Thieme (submitted)). Notably, where the HTP is a functional predator (i.e. infected individuals neither recover nor reproduce, Boots (2004)) there is always a greater opportunity for the VT symbiont persist compared with when the HTP acts like a true parasite (i.e. infected individuals can recover and can reproduce; Jones et al. 2007). This is because in a ‘predatory’ system, HTP-infected hosts do not contribute to the population of susceptible hosts, and the susceptible hosts are therefore less able to compete for resources with the population of VT symbiont-infected hosts. The VT symbiont-infected hosts can therefore provide a lower level of protection to the host from the HTP and still persist in the system (Jones et al. 2007). Overall, therefore, theory predicts that interference between VT symbionts and HTPs is possible. There is mounting empirical evidence that this possibility is realized in nature.

3. Empirical evidence for VT symbiont involvement in host resistance to natural enemies

As a result of increased awareness of the incidence of symbionts and hence more general screening for their presence in host study organisms, there has been a dramatic increase in the evidence for symbiont-mediated protection over the past 5 years. This evidence can broadly be divided into evidence for symbionts (a) protecting their host from microbial diseases, (b) protecting their host from parasites and (c) protecting their host from predators (summarized in table 1).

Table 1
Summary of empirical studies finding direct evidence for symbiont-mediated protection against natural enemies. (The symbiont, host and natural enemy in each interaction are listed, along with the protection mechanism where known.)

(a) Provision of protection from pathogens

Symbiotic microbes have the capacity to protect their hosts from pathogenic micro-organisms, and there is evidence for symbiont protection in diverse arthropods including shrimp, lobster, aphids and mosquitoes. For example, symbionts produce antifungal metabolites that protect their crustacean hosts Palaemon macrodactylus and Homarus americanus from the pathogenic fungus Lagenidium callinectes (Gil-Turnes et al. 1989; Gil-Turnes & Fenical 1992). Similarly, possession of the facultative symbiont Regiella insecticola is associated with host resistance to a fungal pathogen Pandora neoaphidis in aphids (Ferrari et al. 2004; Scarborough et al. 2005). Another interesting phenomenon is that the cardia of the Anopheles gambiae gut expresses several anti-Plasmodium factors (Warr et al. 2007). Research is currently underway that suggests that the presence of the natural bacterial flora in the mosquito ‘primes’ or activates the immune response against Plasmodium in addition to having a direct effect on parasite development in the mosquito gut (G. Dimopoulos 2007, personal communication). The mosquito's capacity to transmit malaria is therefore likely to be significantly influenced by its microbial exposure in nature.

(b) Provision of protection from parasites

In addition to protecting their hosts from other micro-organisms, symbionts may also protect their hosts from parasitic invertebrates, and there are two examples that support this. First, in the pea aphid, Acyrthosiphon pisum, two facultative symbionts, Serratia symbiotica and Hamiltonella defensa, confer protection to their host from the parasitoids Aphidius ervi and Aphidius eadyi (Oliver et al. 2003, 2005; Ferrari et al. 2004). Second, gammarid crustaceans can be infected by Acanthocephala (parasitic helminths). Gammarids are the intermediate hosts in which the helminths develop until a point when they manipulate their host's behaviour to make it more likely to be predated by the helminth's definitive host (Bauer et al. 2005). However, when the gammarid is also infected by microsporidian symbionts, the microsporidia reduce the behavioural manipulation by the helminth parasite, effectively reducing the predation risk to their host (Haine et al. 2005; Rigaud & Haine 2005). This helminth parasite only partially castrates its gammarid host, therefore by ‘sabotaging’ the behavioural change, the microsporidia must gain enough advantage in terms of increased host survival to offset the costs of interference. Interestingly, the examples in this section are where the parasite is a functional predator and these are predicted to be more likely to allow the persistence of VT symbionts than true parasites (Jones et al. 2007).

(c) Provision of protection from predators

Finally, there is evidence that symbionts can produce toxic compounds that protect their hosts from predators. Kellner (1999) first proposed that endosymbionts in Paederus beetles produce the polyketide toxin pederin, rather than the beetles themselves. This toxin confers protection to Paederus beetle larvae from wolf spiders (Kellner & Dettner 1996). Pederin was subsequently confirmed to originate from a bacterial symbiont of the beetles, rather than the beetles themselves (Kellner 2001, 2002; Piel 2002; Piel et al. 2004a). Polyketide toxins like pederin are also found in sponges and although at least one of these toxins is of bacterial origin (Faulkner et al. 1999; Piel et al. 2004b), as yet there is no link between polyketides and sponge defences against predators. However, another polyketide produced by the bacterial symbiont Endobugula sertula deters fishes from predating its bryozoan host (Davidson et al. 2001; Lopanik et al. 2004a,b), and a similar symbiont-mediated mechanism is thought to protect marine isopods from fish predation (Lindquist et al. 2005).

4. Mechanisms of symbiont-mediated protection

The mechanisms by which symbionts protect their hosts from natural enemies are diverse. As described above, some produce substances with antimicrobial properties such as isatin (Gil-Turnes et al. 1989) and tyrosol (Gil-Turnes & Fenical 1992). Others deter potential predators from their hosts (Kellner & Dettner 1996; Lopanik et al. 2004b) through the production of toxic compounds called polyketides, such as bryostatin (Lopanik et al. 2004a), pederin (Piel 2002), and onnamides and theopederins (Piel et al. 2004b), which can inhibit eukaryotic protein biosynthesis (e.g. Tiboni et al. 1968). In addition, it has recently been proposed that a toxin produced by the bacteriophage APSE in the symbiont H. defensa may be the mechanism by which this symbiont protects its aphid host from parasitoids (Moran et al. 2005). This toxin is similar to Shiga toxin, which disrupts eukaryotic cell processes. It would be interesting to determine whether S. symbiotica, the other symbiont that protects aphids from parasitoid attack, and R. insecticola, which protects aphids from fungal pathogens, also possess bacteriophages with similar toxin-producing capabilities. By contrast, the mechanism by which microsporidia sabotage the behavioural change induced in gammarids by Acanthocephala remains unclear. Acanthocephala manipulate host behaviour in some gammarid species by altering serotonergic activity (Tain et al. 2006), and the microsporidia possibly interferes with this process rather than by directly killing the other parasite, since the Acanthocephala infecting gammarids that are also infected by microsporidia are viable (Haine et al. 2005).

It is likely that there are other (hypothetical) mechanisms by which VT symbionts protect their hosts. For example, in addition to producing growth-inhibiting toxins, symbionts might also directly protect their hosts by outcompeting HTPs for host resources. Alternatively, they may indirectly protect their host by preventing superinfection of the host by HTPs, perhaps by altering host behaviour or augmenting host defences to prevent disease establishment. In all these cases, however, it is essential that symbionts are able to avoid host immune defences. There are three reasons why this is necessary: first, VT symbionts must avoid recognition by the host immune system in order to establish and be maintained in the host; second, where the host is superinfected by a parasite, they must survive the parasite-induced immune response; and third, if the VT symbiont manipulates the host immune defences to overcome a parasite it must also survive the augmented immune response. A tantalizing possibility is that VT symbionts may have the capacity to commandeer host defences to produce a swifter response to a HTP than the host on its own.

5. VT symbiont interactions with host immune defences

Hosts are selected to identify invading micro-organisms and swiftly mount immune defences in order to eliminate pathogens. Where the maintenance of a VT symbiont provides the host with a defence advantage, the host must exercise balance between recognizing and defending itself against HTPs, and maintaining beneficial VT symbionts. A VT symbiont may therefore be under selection to avoid being recognized by its host immune system, but at the same time it must not suppress its host's immune defences against pathogens. A VT symbiont's capacity to protect its host from natural enemies and its capacity to avoid its host's immune defences are therefore intrinsically linked. It is therefore essential to explore the interactions between symbionts and their host immune defences in order to understand symbiont-mediated protection.

Despite only possessing innate immune defences (Siva-Jothy et al. 2005), invertebrates are able to defend themselves against, and survive, a wide variety of parasites (Poulin 2007). They do this through the sophisticated management of the cellular and humoral components of their immune systems (reviewed in Loker et al. 2004; Little et al. 2005; Siva-Jothy et al. 2005). Their first line of defence comprises barrier defences—cuticle and gut. If these barrier defences are breached, perhaps via a wound, then cellular processes such as phagocytosis, nodulation and encapsulation quickly surround invading pathogens, physically separate them from the haemocoel and kill them (e.g. Cherry & Silverman 2006). Meanwhile a suite of humoral defences are expressed—antimicrobial peptides (AMPs; Bulet et al. 2004), phenoloxidase (Suguraman 2002) and coagulation (Theopold et al. 2004). Together these defences serve to eliminate any invading parasites or pathogens and physically separate them from the haemocoel. All of these components are relevant to the entry, establishment and persistence of VT symbionts in their hosts, and it is possible that they may also be manipulated by symbionts in order for the VT symbiont to evade, suppress or even upregulate host immune responses.

A straightforward strategy to avoid being recognized by the host immune response is for a symbiont to locate itself inside host cells, where AMPs and other components of haemolymph-based invertebrate immune responses cannot penetrate. Indeed, most VT symbionts are obligately intracellular, having lost the capacity to exist in a free-living state during the evolutionary history of their association with their hosts (e.g. McGraw & O'Neill 2004). A small number of studies have examined the interactions between VT symbionts and invertebrate immunity (table 2). Studies on Wolbachia suggest either that there are particular host-genotype/symbiont-genotype interactions that determine whether or not the symbionts interfere with host defences, or that the symbiont only interacts with some, but not all, components of the host immune system (Bourtzis et al. 2000; Fytrou et al. 2005; Pankewitz et al. 2007). For example, Wolbachia reduced the ability of Drosophila simulans to encapsulate eggs of the parasitoid Leptopilina heterotoma, but had no impact on host resistance to an entomopathogenic fungus (Fytrou et al. 2005). Other VT symbionts fail to elicit several different components of their host immune responses (Rickettsia: Mattila et al. 2007, in press; Spiroplasma: Hurst et al. 2003), but while VT symbionts such as Spiroplasma can evade recognition by the host immune system, activation of host defences results in suppression of its titre (Hurst et al. 2003). By contrast, the tsetse fly (Glossina morsitans morsitans) is infected by three VT symbionts, Wigglesworthia, Sodalis and Wolbachia, but their densities did not change when the host immune system was activated by a challenge with Escherichia coli (Rio et al. 2006). However, some VT symbionts elicit host immune defences (Heddi et al. 2005) and this may be a strategy the host uses to control symbiont numbers and location (Anselme et al. 2006). Others are refractory to AMPs compared to their free-living relatives (Hao et al. 2001; Baldridge et al. 2005; Hu & Aksoy 2005), but the mechanism of this resistance is unknown. The general mode of action of AMPs is to be bactericidal: they are attracted to negatively charged phospholipids in cell membranes where they form pores or channels that disrupt membrane potential and result in cell death (Zasloff 2002). It is tempting to speculate that VT symbionts can alter their membrane charge, so they are less susceptible to binding by positively charged AMPs.

Table 2
Symbiont avoidance of host defences. (In each case, the symbiont and host are listed, along with the defence component that has been investigated with regard to the interactions between symbionts and host immunity. ‘Yes’ and ‘no’ ...

VT symbionts may evade recognition by the receptors that trigger synthesis of AMPs by losing the surface molecules that elicit immune gene expression or by hiding behind host-derived surface molecules. For example, symbiotic Mollicutes such as spiroplasmas completely lack cell walls (Trachtenberg 1998), and it is the recognition of the constituents of microbial cell wall components such as peptidoglycan that results in the production of AMPs (Leulier et al. 2003). The lack of a cell wall may therefore explain their inability to activate the production of AMPs in Drosophila (Hurst et al. 2003) and could provide a reason why, compared with many VT symbionts, Spiroplasma are able to survive freely in the haemolymph and not just inside host cells. By contrast, Wolbachia are present in their hosts enclosed in a vacuole enveloped by three layers of membrane, the outer of which is derived from their host (Louis & Nigro 1989). They may therefore evade recognition as non-self by effectively hiding behind a host-derived cloak. Alternatively, VT symbionts may continually vary their surface antigens to avoid recognition. Some VT symbiont surface molecules are under positive selection and may even have been lost in some certain lineages (Schulenberg et al. 2000; Blanc et al. 2005; Jiggins 2006). However, Jiggins et al. (2002) found that there is positive selection on an outer membrane protein in parasitic, but not mutualistic, Rickettsiaceae, and this suggests that host evasion strategies may vary with the position of the VT symbiont on the parasitism–mutualism continuum. A recent review by Finlay & McFadden (2006) gives a comprehensive overview of how pathogens might evade host immune systems and many of the processes described in their review are relevant to VT symbionts.

Considering that VT symbionts can evade invertebrate immune defences and have the potential to manipulate them, invertebrate immune effector systems are likely to be an important line of defence at which the conflict between VT symbionts and HT natural enemies is fought. The capacity of an invertebrate to mount an immune response to pathogens, with and without infections by VT symbionts, should therefore be added to the ‘traditional’ measures of fecundity, size and longevity as a measure of the fitness consequences of VT symbiont infections.

6. Conclusions

Given the ubiquity of VT symbionts in invertebrates (Stouthamer et al. 1999; Terry et al. 2004; Zchori-Fein & Perlman 2004), it is likely that VT symbiont infections contribute significantly to variation in invertebrate resistance to HTP infections (Schmid-Hempel 2003). Theory predicts a three-way interaction between VT symbionts, natural enemies and their hosts, which is mediated by interference by VT symbionts on the impact that natural enemies have on their hosts. There is mounting empirical evidence that these three-way interactions exist and the routes by which they are mediated are diverse. Symbiont-mediated protection is moving from beyond the realm of obscure one-off occurrences, into a phenomenon that is likely to be widespread, and it goes some way towards explaining why VT symbionts are so common in invertebrate lineages. Interference by VT symbionts may well account for variation in behavioural modifications, pathogen prevalence, immune competence, pathogen virulence and host susceptibility.

Fruitful avenues of research will investigate whether the degree of protection depends on the length of time the host and VT symbiont have been associated, or on particular host genotype—VT symbiont genotype combinations. It would be particularly interesting to investigate whether the protection conferred by VT symbionts against microbial pathogens has arisen as a result of coevolution with a particular pathogen that infects that host or whether the protection is a generalized and systemic response to any pathogen whether it is a specialist on its host or an opportunist. Further detailed investigations of the immune- and predator-defence capabilities of VT symbiont-infected and uninfected invertebrates are likely to yield more examples of interference.

It would be particularly valuable to test the theory behind our understanding of these interactions by exploring how transmission rates of both types of parasite affect the level of protection through interference and its impact on host population dynamics (Jones et al. 2007), and explore the consequences of such interference on disease epidemiology. In addition, it would be interesting to perform general surveys of VT symbiont prevalences and, using natural history data, test the prediction that VT symbionts are more likely to persist in a system containing a functional predator as opposed to a true parasite (Jones et al. 2007). This aspect has potential ecological importance since the interference by VT symbionts (such as those in aphids) with functional predators (e.g. parasitoids) can have implications for food web complexity (Lafferty et al. 2006). Symbiont-mediated protection should also be given special attention in any system being developed for biological control purposes, since a control method developed for a VT symbiont-free population of a pest species might not work as efficiently for a population infected by a VT symbiont. Finally, lateral gene transfer between Wolbachia and its invertebrate hosts has been demonstrated (Kondo et al. 2002; Dunning Hotopp et al. 2007) and this opens up the intriguing possibility that invertebrates can potentially acquire VT symbiont genes, such as those that encode toxins such as pederin, to defend themselves against their natural enemies. It is therefore crucial to consider the presence of VT symbionts (and VT symbiont genes) in any studies that measure the immune competence, predator avoidance or other fitness aspects of invertebrates as they are likely to account for much of the variance measured in many different fitness traits.

Figure 1
Schematic showing the interactions in a system containing a vertically transmitted symbiont (VTP), a host and a HTP (Jones et al. 2007).
Figure 2
Densities at equilibrium of susceptible hosts, HTP- and VTP-infected hosts, with increasing protection provided by the VTP against the HTP (Jones et al. 2007).

Acknowledgments

I am indebted to Jens Rolff, Mike Siva-Jothy and three anonymous referees for useful comments on the manuscript, Thierry Rigaud for inspiration, and I would particularly like to thank Ed Jones and Mike Boots for their help on the theoretical considerations. Many thanks are also due to George Dimopoulos, Josh Mattila and Horst Thieme for access to pre-publication manuscripts and data.

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