Bacterial mechanism of immune avoidance

There are two types of solution to the 'problem' of the host immune system. The first is to limit the time spent outside of cells. The second is to evolve mechanisms that either stop induction of host immunity, or be insensitive to the host systems.

The former—limited time in the haemolymph— appears to be the strategy adopted by Riesia, the primary symbiont of lice. Although it would not be advantageous for a host to attack a beneficial symbiont, it does appear to occur in this case. Observations by Perotti and coworkers of the migration of Riesia out of the bacteriome into the ovary record the bacterium being 'chased by hemocytes' (Perotti et al, 2007). As the bacteria are released from the cells of the stomach disk, and migrate to the ovariole, they are pursued by haemocytes which attempt to engulf them. The bacteria form pores in the tunica surrounding the ovariole, each pore being then covered by a haemocyte. Perotti et al. note that the host is morphologically adapted to the bacterium—including surface properties of the tunica that aid adhesion and entry—but very poorly adapted in terms of immunological co-operation. Riesia survives by possessing a surprising turn of speed.

SZPE, the primary symbiont of Sitophilus weevils, also appear to survive through limited time spent outside cells. As previously noted, SZPE moves from the bacteriome to the haemocoel during the nymphal phase, from where it invades the ovary. Experiments have demonstrated that SZPE injected into the haemocoel is recognized as an invader that does upregulate the host immune cascades (Anselme et al., 2008). Thus, despite SZPE being a required symbiont, the haemocoel is a hostile environment to it during its passage through it.

Other bacteria—notably secondary symbionts such as Arsenophonus, Spiroplasma, Serratia, Sodalis, and Hamiltonella—spend considerable periods of time outside cells, and thus must either not induce host responses or be insensitive to the systems. This has been examined in the case of S. poulso-nii infecting Drosophila in vivo, and for the case of Sodalis in tsetse flies, in vivo and in vitro.

For the S. poulsonii-Drosophila interaction, no induction of AMPs was observed in this system (Hurst et al., 2003), and a lack of generalized immune activation was corroborated by micro-array studies (G.D.D. Hurst, unpublished results). Ectopic immune activation did appear to reduce Spiroplasma titre in this system, implying that the organism did not induce host defences, but was susceptible. It is notable that spiroplasmas are like all mollicutes in possessing virtually no polysac-charide cell coat, and this may be a reason why they do not elicit a response.

For Sodalis, in contrast, titre is unaffected by ectopic immune activation. When the tsetse system of humoral immunity was upregulated through feeding with pathogens, there was no observable reduction in the titre of Sodalis (Rio et al., 2006). Sodalis exists intracellularly (in the gut epithelia) and also free in the haemolymph. Experiments indicate that Sodalis in vitro is not strongly affected by tsetse AMPs (Hao et al, 2001; Hu and Aksoy, 2005). Indeed, tsetse flies constitutively express a homologue of diptericin, which has been suggested to be a result of exposure to symbionts throughout the host life history (Hao et al., 2001).

The 'lack of coat' explanation for failure of spiroplasmas to elicit an immune response is a conjecture. It is unlikely to be generally true of haemolymph-associated bacteria, as Arsenophonus, Serratia, Hamiltonella, and Sodalis are all gamma proteobacteria likely to carry significant cell walls, just as Photorhabdus does. Whereas alteration of their coat as a means of reducing the host response is possible, perhaps most likely is that they, like Photorhabdus, also have means of surviving when phagocytosed and of inhibiting phagocytosis, combined with a means of either downregulating AMP production or resisting the effects of AMPs. Photorhabdus, for instance, can induce apoptosis in haemocytes through the gene mcf (Daborn et al., 2002), and secretes unidentified diffusible molecules that reduce phagocytosis (Au et al, 2004), protecting the bacterium against cellular immunity.

The genomes of these bacteria do suggest some candidate molecules for interaction with the immune system. The genome of A. nasoniae, for instance, possesses a homologue of ecotin, within the operon of a type-three secretion system (making it highly likely to be a secreted peptide) (T. Wilkes, A.C. Darby, and G.D.D. Hurst, unpublished results). Ecotin encodes a protein belonging to the serine protease inhibitor class. Serine protease inhibitors (serpins) operate in many host systems as inhibitors of response cascades initialized by serine proteases. Ecotin has been demonstrated to be able to inhibit host processes that are initiated by protease activation, such as blood clotting (Castro et al, 2006). Perhaps most interestingly, ecotin has been observed to affect the ability of neutrophils to neutralize ingested E. coli. In vitro studies indicate that elastase, a serine protease secreted into the phagolysosome by neutrophils, is inhibited by ecotin (Eggers et al., 2004). Whereas a role for Arsenophonus ecotin as a general mechanism of resisting protease activity cannot be discounted (the bacterium does need to resist proteases encountered in gut transit to enter the haemocoel, and probably also needs to be able to inhibit its own arsenal of secreted proteases), a role for this gene in inhibiting elicited defence cascades is tempting, and worthy of investigation. The genome of A. nasoniae contains other genes whose homologues are known to function in the inhibition of phagocytosis, such as cytotoxic necrotizing factor 1 (T. Wilkes, A.C. Darby, and G.D.D. Hurst, unpublished results).

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book

Post a comment