Immunocompetence of Galleria mellonella: sex- and stage-specific differences and the physiological cost of mounting an immune response during metamorphosis

The antibacterial immune response of the wax moth, Galleria mellonella, was analysed by use of an inhibition zone plate assay. We demonstrated significant stage-specific differences as the immune response was most effective in the pupal, next the larval and then the adult stage. In addition, we demonstrated that an immune challenge at the onset of, or during metamorphosis does not increase nor decrease the strength of the antibacterial immune response in the subsequent developmental stage(s). These findings illustrate that induced immunity is not preserved during metamorphosis but also deny any cost to the immune system itself. However, an immune challenge does induce a significant shortening of the direct development time and affects the mass loss during metamorphosis in a sex-dependent manner: males emerged smaller whereas the mass of females was not significantly affected. These observations indicate that there are sex-specific costs to mounting an immune response during metamorphosis which affect physiological traits, implicating a trade-off between immunity and development.     

Population-level variation of digestive physiology costs of mounting an immune response in damselflies

1. Trade-offs are often predicted to occur between energetically costly activities, such as somatic growth and eliciting immune responses to parasites. Although parasitism frequently reduces growth via lowered consumption, it remains unclear if the energetic demands of generating immune responses also affect the digestive physiological processes necessary for growth. Moreover, as local environmental conditions affect energetic investment towards growth and immune responses, the extent of any digestive–immune response trade-offs may vary among populations and not be fixed at the species-level. 2. To test these ideas, melanisation – a general innate immune response – was first induced in damselfly larvae (Enallagma vesperum) from two populations. The study then quantified growth and consumption rates, assimilation and production efficiencies, and daily metabolic rates to determine if digestive–immune response trade-offs were present and, if so, whether they differed between populations. 3. There was no evidence of any trade-offs between immune responses and digestive physiology components in either population. However, the results did show that populations differentially allocated energy towards different digestive physiology components after an immune response was elicited: one population increased their relative consumption and daily metabolic rates, while the other population had lower assimilation efficiencies and consumption rates. 4. Although researchers lack a mechanistic understanding of the observed population-level differences, these results suggest that accounting for population-level variation in digestive physiology and immune responses is critical to inferences about how immunological defences to parasitism may affect the ability for organisms to both acquire and utilise resources.     

The role of interleukin 15 in mounting an immune response against microbial infections

Interleukin (IL)-15 is a recently described cytokine that resembles IL-2 in its biological activities, stimulating natural killer cells, T cells and B cells to proliferate, secrete cytokines, and exhibit increased cytotoxicities or produce antibody. IL-15 also exerts unique functions such as stimulation of phagocytes, maintenance of mast cells and migration of activated/memory T cells. IL-15 is involved in protection against infections with a variety of microbes through not only activating innate immunity but also mounting adaptive immunity.     

Does the strength of an immune response reflect its energetic cost?

The energetic cost of immune responses has been proposed to be an important basis for trade-offs between life-history traits, such as between survival and reproduction. A critical assumption of this hypothesis is that the magnitude of the energetic cost increases with the strength of an immune response, so that energy can be saved by partly suppressing a response. Here, we test this assumption experimentally. The immune system of great tits Parus major was experimentally activated by injecting different doses of phytohemagglutinin (PHA) in the wing web. We found the resting metabolic rate of immune challenged birds to increase by 5%. However, although great tits injected with a high dose had a stronger immune response, this was not paralleled by a higher metabolic rate. Thus, we found the energetic cost of the immune response to be relatively low and not dose-dependent. This suggests to us that the energetic cost of immune responses cannot form the basis for trade-offs between life-history traits.     

The costs of mounting an immune response are reflected in the reproductive fitness of the mosquito Anopheles gambiae

We have used Anopheles gambiae , a major vector of malaria in Africa, to test the hypothesis that the operation of a surveillance or immune system against microorganisms and parasites can be costly to the reproductive success of the host. Blood-fed mosquitoes were challenged with an immune elicitor, lipopolysaccharide (LPS), and their resultant antimicrobial activity, accumulation of yolk protein in the ovary and egg production was monitored. Humoral activity against the Gram-positive bacterium Micrococcus luteus was induced by LPS injection in a dose-responsive manner. LPS treatment also caused a concomitant significant reduction in the accumulation of protein in ovaries 24 h after injection and in the production of eggs during the same gonotrophic cycle. Unlike immune stimulation, reduction in reproductive fitness was not dose responsive. Oral administration of LPS also significantly reduced ovarian protein content although we could not detect the presence of anti- M. luteus activity in the gut tissue by using an inhibition zone assay. These findings indicate that immune stimulation imposed reproductive fitness costs on mosquitoes.     

The cost of an immune response: vaccination reduces parental effort

A fundamental assumption of theories of the ecology and evolution of inducible defences is that protective responses to attacks by parasites or predators should not only have benefits, but also costs. The vertebrate immune system is by far the best studied example of an inducible defence, yet little is known about the costs of an immune response, especially in natural populations. To test if an immune response per se is costly, we induced an antibody response in female blue tits, Parus caeruleus , by immunising them with human diphtheria–tetanus vaccine, and compared their nestling-feeding rate with that of saline-injected controls. We found that vaccinated females reduced their nestling feeding rate, thus demonstrating a cost of the immune response in the currency of parental effort.     

No apparent cost of evolved immune response in Drosophila melanogaster

Maintenance and deployment of the immune system are costly and are hence predicted to trade‐off with other resource‐demanding traits, such as reproduction. We subjected this longstanding idea to test using laboratory experimental evolution approach. In the present study, replicate populations of Drosophila melanogaster were subjected to three selection regimes—I (Infection with Pseudomonas entomophila), S (Sham‐infection with MgSO₄), and U (Unhandled Control). After 30 generations of selection flies from the I regime had evolved better survivorship upon infection with P. entomophila compared to flies from U and S regimes. However, contrary to expectations and previous reports, we did not find any evidence of trade‐offs between immunity and other life history related traits, such as longevity, fecundity, egg hatchability, or development time. After 45 generations of selection, the selection was relaxed for a set of populations. Even after 15 generations, the postinfection survivorship of populations under relaxed selection regime did not decline. We speculate that either there is a negligible cost to the evolved immune response or that trade‐offs occur on traits such as reproductive behavior or other immune mechanisms that we have not investigated in this study. Our research suggests that at least under certain conditions, life‐history trade‐offs might play little role in maintaining variation in immunity.     

A Src-astic response to mounting tension.

The nerve growth cone binds to a complex array of guidance cues in its local environment that influence cytoskeletal interactions to control the direction of subsequent axon outgrowth. How this occurs is a critical question and must certainly involve signal transduction pathways. The paper by Suter and Forscher (2001)(this issue) begins to address how one such pathway, an Src family tyrosine kinase, enhances cytoskeletal linkage to apCAM, a permissive extracellular cue for Aplysia growth cones. Interestingly, they show that applied tension increases this kinase's localized phosphorylation that in turn further strengthens linkage. This suggests a potential positive feedback mechanism for amplifying and discriminating guidance information to guide growth cone motility.     

A landscape for the dynamics of an immune response

Dynamic shaping of the antibody repertoire is essential for effective immunity. We describe here a novel approach for clarifying how the antibody repertoire is shaped over time for development of a specific immune response. We obtained over 500 immunoglobulin G1 clones harboring VH186.2 from the spleen, bone marrow, and microdissected individual germinal centers of (4-hydroxy-3-nitrophenyl) acetyl-immunized C57BL/6 mice at various time points postimmunization. Statistical analyses provided an index for defining clonal diversity and cluster analyses gave us a three-dimensional landscape with which clone distance was visualized with the expression level of antibodies. This landscape approach facilitated our understanding of the dynamics shaping the actual antibody repertoire, in which pre-existing naturally occurring population persisted and provided a significant impact upon the repertoire. To the established model for describing production of the antibody-forming cells, we were able to append an indispensable issue in considering the maturation of humoral immune response.     

Intensity of the humoral immune response to herpesviruses as an indicator the body immune deficiency

The state of the local immunity system of the oral cavity was studied by the level of saliva immunoglobulins in patients with different processes on their mucous membranes: herpetic infection, respiratory allergosis and malignant tumors of the mouth cavity and the laryngopharynx. The suppression of the production of sIgA, was accompanied by the enhanced production of antibodies to the most widespread herpesviruses (herpes simplex virus, cytomegalovirus and Epstein-Barr virus). The maximum levels of serum IgG to herpesviruses were determined in patients with malignant tumors. The role of herpesviruses in the pathogenesis of immunodeficient states is discussed.     

ISG20, an actor of the innate immune response

The interferon (IFN) system is a major effector of the innate immunity that allows time for the subsequent establishment of an adaptive immune response against wide-range pathogens. The effectiveness of IFN to control initial infection requires the cooperation between several pathways induced in the target cells. Recent studies that highlight the implication of the 3'-5' exonuclease ISG20 (IFN Stimulated Gene product of 20 kDa) in the host's defenses against pathogens are summarised in this review.     

Decreased immune response as a proximate cost of copulation and oviposition in a damselfly

Abstract.Males and females of the Japanese calopterygid damselfly, Matrona basilaris japonica Fester, showed a rapid (within 24 h), and significant reduction in immune system function (encapsulation response) after reproductive activity (copulation or oviposition).
 A similar, but non‐significant, change occurred in males that conducted energetically costly behaviour (fighting).
 These data suggest that there may be physiological costs other than energy‐based trade‐offs associated with copulation and oviposition that may have life‐history consequences via their effects on immune system function.     

Energetic and developmental costs of mounting an immune response in greenfinches (<Emphasis Type="Italic">Carduelis chloris</Emphasis>)

It is assumed that there is a trade-off between the costs allocated to mounting an immune defence and those allocated to costly functions such as breeding and moulting. The physiological basis for this is that mounting an immune response to pathogen challenge has energetic and/or nutrient costs which may interfere with metabolic processes of the challenged individual. If the energetic costs of mounting an immune response are not too high, animals may face such costs by increasing their acquisition of food energy, suggesting that limited nutrients may be responsible for the costs of immune defence. We assessed the energetic and developmental costs of mounting an immune response in an experiment in captivity with first-year greenfinches (Carduelis chloris) challenged with sheep red blood cells and Brucella abortus. Antibody production against both antigens increased the daily energy expenditure (4.7%) of immune-challenged birds relative to control birds, although the difference was non-significant. We estimated that the maximum effect size supported by the data would be 9.9% higher in immune-challenged birds relative to control birds. We plucked the two outermost rectrices of each bird to assess the effects of the immune challenge on growth of the regenerated feathers. The immune challenge had no significant effect on the length of the regenerated rectrices. However, these feathers were more asymmetric in length in immune-challenged birds than in control birds. Although first-year male greenfinches paid a relatively low energetic cost when mounting an immune response, we suggest that immune-challenged individuals may have paid some costs over the long term based on the increased fluctuating asymmetry in the developing feathers.     

Thyrotropin: an endogenous regulator of the in vitro immune response

We have previously shown that thyrotropin (TSH), which is produced by lymphocytes in response to the T cell mitogen staphylococcal enterotoxin A, enhances in vitro antibody production to T cell-dependent and independent Ag (SRBC and trinitrophenylated Brucella abortus [BA-TPN], respectively) as determined by a direct plaque-forming cell assay. As a result of these studies, experiments were designed to examine the possible immunoregulatory function of thyrotropin-releasing hormone (TRH) on the in vitro antibody response to the T cell-independent Ag BA-TNP. Our studies demonstrate that TRH at very low concentrations (pM) enhances the in vitro plaque-forming cell response to BA-TNP and also induces splenocyte production of TSH. Other hypothalamic-releasing factors were without effect. This enhancement effect by TRH was specifically blocked by rabbit antisera to the TSH-beta subunit, whereas addition of normal rabbit sera had no effect. These data suggest that TRH specifically enhances the in vitro antibody response via production of immunoreactive TSH.     

Maturation of the humoral immune response as an optimization problem.

Efficient immune response often depends on the production of high affinity antibodies. We show analytically that the optimal strategy for a fast production of high affinity antibodies is to utilize a step-function mutation rate, i.e. a minimal mutation rate in early stages of the immune response, followed by a discontinuous switch to the maximal possible rate when the proliferating population of B-cells exceeds a threshold value. Our results are in accordance with the biological observations concerning the time of onset of the hypermutation process, and with the mutation rate during the later stages of the primary immune response. Indeed the hypermutation process plays a crucial role in responding to a prevailing pathogen at each round of immune response, and not only for coping with future infections. Moreover, as the effect of hypermutations is shown to be crucially dependent on the number of proliferating B-cells, its onset is not expected to depend on an external signal, but rather to be related to the clone's age. This suggests that the onset is host species specific, rather than pathogen specific. Another implication of the present results is that activation of hypermutations before the B-cell population has reached the critical size may impede the efficiency of the response.