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Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells.

Chemokines compose a sophisticated communication system used by all our cell types, including immune cells. Chemokine messages are decoded by specific receptors that initiate signal transduction events leading to a multitude of cellular responses, leukocyte chemotaxis and adhesion in particular. Critical determinants of the in vivo activities of chemokines in the immune system include their presentation by endothelial cells and extracellular matrix molecules, as well as their cellular uptake via "silent" chemokine receptors (interceptors) leading either to their transcytosis or to degradation. These regulatory mechanisms of chemokine histotopography, as well as the promiscuous and overlapping receptor specificities of inflammation-induced chemokines, shape innate responses to infections and tissue damage. Conversely, the specific patterns of homeostatic chemokines, where each chemokine is perceived by a single receptor, are charting lymphocyte navigation routes for immune surveillance. This review presents our current understanding of the mechanisms that regulate the cellular perception and pathophysiologic meaning of chemokines.

Animals↗

The crucial role of systemic responses in the innate (non-adaptive) host defense.

We suggest that successful defense against microbial invasion requires both local inflammation and systemic anti-inflammation. The key systemic responses involve the hypothalamic-pituitary-adrenocortical axis, the sympathetic-adrenomedullary axis, acute phase protein production, thermoregulation and alterations in leukocyte responsiveness to agonists such as bacterial endotoxin. These integrated responses raise blood and tissue concentrations of several anti-infective molecules, mobilize leukocytes into the circulation, and increase blood flow to injured or infected sites. They also neutralize cytokines, proteases and oxidants that enter the bloodstream from inflamed local sites and forestall endothelial activation in distant vessels. Together, these forces help concentrate activated phagocytes at injured or infected local sites while preventing potentially damaging inflammation in uninvolved tissues.

Animals↗

Host parasite relationships in Trypanosoma (duttonella) vivax with special reference to the influence of antigenic variation.

A mouse model system was used to study various aspects of host and parasite relationships in Trypanosoma vivax infections. These included the phenomenon of antigenic variation, the variable parasite antigens responsible for this phenomenon, parasite-host adaption, host immune responses and the role of genes in the major histocompatibility complex in the control of infection. While the mouse model system has allowed investigation of these aspects of host parasite relationships, it is clear that the system is much more limited than those generally used in T. brucei spp and T. congolense infections. This is indicated by the discovery that not all VATs of T. vivax were equally infective for mice, though in some cases infectivity could be improved by bovine serum supplementation and/or immunosuppression of the mouse host. In the case of rats, infection was even restricted to a smaller number of the VATs studied. It was, however, possible to biochemically characterize the variable surface antigen carried by T. vivax and show its similarity to those carried by T. brucei and T. congolense. The H-2 complex was found not to influence acquired resistance of inbred strains. Cyclic transmissions of T. vivax infections to goats combined with chemotherapy were carried out in an attempt to induce protection to subsequent infection as has been shown in T. brucei and T. congolense infections. Such protection could, however, not be obtained, The failure of the metacyclic VATs to induce immunity, was perhaps due to rapid decrease in antibody titres to bloodstream VATs found after treatment and prior to rechallenge. The usefulness of the mouse model system in elucidating the mechanisms responsible for the non-H-2 linked differences in susceptibility to T. vivax infections should be further explored and its relevance to mechanisms of trypanotolerance in domestic ruminants defined.

Animals↗

Recent developments in Campylobacter pathogenesis.

PURPOSE OF REVIEW: The Campylobacter species jejuni and coli are leading causes of enteritis and enterocolitis worldwide. Arthritis, Reiter syndrome, and Guillain-Barré syndrome represent post-infectious sequelae. Although the acute and chronic clinical manifestations highlight Campylobacter species as excellent models for the identification of mechanisms involved in pathogenesis, detailed investigations at the molecular level are complicated by the fastidious growth requirements of the bacteria and by the tremendous variability displayed by Campylobacter isolates. Thus, research activities in this field constitute a substantial challenge for scientists of many different disciplines. The genome information has greatly stimulated investigations at the molecular level and the resulting modern research trends lead to a better understanding of Campylobacter-associated diseases providing the basis for new developments in prevention and therapy. RECENT FINDINGS: This review summarizes results from the most recent investigations in the field of Campylobacter pathogenesis. Topics include genome analysis, surface structures and post-infectious complications, adaptation, host cell interaction and cell toxicity. SUMMARY: During its coevolution with human and other vertebrate hosts, Campylobacter species have developed specific survival strategies, which are required for host adaptation and establishment in the intestinal environment. The bacterial factors involved in these processes are the subject of intensive research activities. With a focus on molecular aspects of the most important human pathogen, C. jejuni, this review intends to summarize the recent trends and developments in Campylobacter research by highlighting selected publications in the field of microbial pathogenesis.

Arthritis, Reactive↗

A pox on thee! Manipulation of the host immune system by myxoma virus and implications for viral-host co-adaptation.

The poxviruses have evolved a diverse array of proteins which serve to subvert innate and adaptive host responses that abort or at least limit viral infections. Myxoma virus and its rabbit host are considered to represent an ideal poxvirus-host system in which to study the effects of these immunomodulatory proteins. Studies of laboratory rabbits (Oryctolagus cuniculus) infected with gene knockout variants of myxoma virus have provided compelling evidence that several myxoma virus gene products contribute to the pathogenic condition known as myxomatosis. However, myxomatosis, which is characterized by skin lesions, systemic immunosuppression, and a high mortality rate, does not occur in the virus' natural South American host, Sylvilogus brasiliensis. Moreover, in Australia where myxoma virus was willfully introduced to control populations of O. cuniculus, myxomatosis-resistant rabbits emerged within a year of myxoma virus introduction into the field. In this review I discuss the characterized immunomodulatory proteins of myxoma virus, their biochemical properties, their pathogenic effects in laboratory rabbits, the role of the host immune system in the susceptibility or resistance to myxomatosis, and the evidence that immunomodulatory genes may have been attenuated during the co-adaptation of myxoma virus and O. cuniculus in Australia.

Adaptation, Physiological↗

Adaptation of the Lyme disease spirochaete to the mammalian host environment results in enhanced glycosaminoglycan and host cell binding.

The Lyme disease spirochaete, Borrelia burgdorferi, is transmitted to mammals by Ixodes ticks and can infect multiple tissues. Host cell attachment may be critical for tissue colonization, and B. burgdorferi cultivated in vitro recognizes heparin- and dermatan sulphate-related glycosaminoglycans (GAGs) on the surface of mammalian cells. To determine whether growth of the spirochaete in the mammalian host alters GAG binding, we assessed the cell attachment activities of B. burgdorferi grown in vitro or in dialysis membrane chambers implanted intraperitoneally in rats. Host-adapted B. burgdorferi exhibited approximately threefold better binding to purified heparin and dermatan sulphate and to GAGs expressed on the surface of cultured endothelial cells. Three B. burgdorferi surface proteins, Bgp, DbpA and DbpB, have been demonstrated previously to bind to GAGs or to GAG-containing molecules, and we show here that recombinant derivatives of each of these proteins were able to bind to purified heparin and dermatan sulphate. Immunofluorescent staining of in vitro-cultivated or host-adapted spirochaetes revealed that DbpA and DbpB were present on the bacterial surface at higher levels after host adaptation. Recombinant Bgp, DbpA and DbpB each partially inhibited attachment of host-adapted B. burgdorferi to cultured mammalian cells, consistent with the hypothesis that these proteins may promote attachment of B. burgdorferi during growth in the mammalian host. Nevertheless, the partial nature of this inhibition suggests that multiple pathways promote mammalian cell attachment by B. burgdorferi in vivo. Given the observed increase in cell attachment activity upon growth in the mammalian host, analysis of host-adapted bacteria will facilitate identification of the cell binding pathways used in vivo.

Adaptation, Physiological↗

Virus and host-specific adaptations in the BL1 and BR1 genes of bipartite geminiviruses.

The host range of individual geminiviruses may be quite narrow, and closely related viruses can exhibit distinct host adaptations. Two such bipartite geminiviruses are bean golden mosaic virus (GBMV) and tomato golden mosaic virus (TGMV). In both, the BL1 and BR1 genes are required for the spread of virus infection in plants. We have investigated the contributions of BL1 and BR1 to host-specific phenotypes of BGMV and TGMV by constructing hybrid viruses in which these coding regions were exchanged. Hybrids were assayed on bean, a good host for BGMV, and Nicotiana benthamiana, a good host for TGMV. A BGMV hybrid having TGMV BL1 and BR1 efficiently infected beans, but elicited attenuated symptoms. In N. benthamiana, this hybrid had slightly increased virulence and DNA accumulation relative to wild-type BGMV. A TGMV hybrid having BGMV BL1 and BR1 was virulent in N. benthamiana, but elicited attenuated symptoms. However, this hybrid exhibited no gain of function in beans relative to wild-type TGMV. Hybrid viruses with TGMV BL1 and BGMV BR1 had severely defective phenotypes in either viral or host background. Although exchanging BL1 and BR1 between BGMV and TGMV did not change host range, some host adaptation of these genes is suggested. However, virus-specific compatibility between BL1 and BR1 is of more importance for viability. Thus, these gene products may act in concert to potentiate virus movement.

Adaptation, Physiological↗

Antigenic alteration of influenza B virus associated with loss of a glycosylation site due to host-cell adaptation.

Effects of host-cell adaptation of the hemagglutinin (HA) protein were evaluated by the analyses of four pairs of recent influenza B field isolates, each pair consisting of an Madin Darby canine kidney (MDCK)- and an embryonated chicken egg-derived isolates from the same clinical specimen. Among the isolates examined, all of the MDCK-derived isolates retained glycosylation site at amino acid 197 on the HA1 molecule, whereas three egg-derived isolates lost it. Antigenic difference in the HA molecule between an MDCK- and an egg-derived isolates of three of these pairs was demonstrated to be associated with the glycosylation 197. Replication of the MDCK-derived isolates was suppressed in eggs, suggesting that the presence of the glycosylation 197 was disadvantageous to replication in eggs. Virus-binding affinity assay revealed that the loss of carbohydrate chain did not significantly alter the preferential recognition of sialic acid linkage. Immunogenicity and vaccine efficacy of an MDCK- and an egg-derived clones of B/Akita/27/2001, the former retained the glycosylation 197 and the latter lost it, were compared in a hamster model. When formalin-inactivated whole virion vaccines prepared from the paired isolates were administered into hamsters, no significant difference between them was observed in protective ability against challenges by the homologous and heterologous clones. Implication of the egg adaptation of influenza virus to antigenic surveillance of the field isolates as well as the selection of vaccine strains, and possibility of the involvement of the viral protein(s) other than the HA in the egg adaptation were discussed.

Animals↗

Evolutionary reversals during viral adaptation to alternating hosts.

Experimental adaptation of the bacteriophage phiX174 to a Salmonella host depressed its ability to grow on the traditional Escherichia host, whereas adaptation to Escherichia did not appreciably affect growth on Salmonella. Continued host switching consistently exhibited this pattern. Growth inhibition on Escherichia resulted from two to three substitutions in the major capsid gene. When these phages were forced to grow again on Escherichia, fitness recovery occurred predominantly by reversions at these same sites, rather than by second-site compensatory changes, the more frequently observed mechanism in most microbial systems. The affected residues lie on the virion surface and they alter attachment efficiency, yet they occur in a region distinct from a putative binding region previously identified from X-ray crystallography. These residues not only experienced high rates of evolution in our experiments, but also exhibited high levels of radical amino acid variation among phiX174 and its known relatives, consistent with a history of adaptation involving these sites.

Adaptation, Physiological↗

Host-plant adaptation drives the parallel evolution of reproductive isolation.

Parallel evolution of similar traits in independent populations that inhabit ecologically similar environments strongly implicates natural selection as the cause of evolution. Parallel speciation is a special form of parallel evolution where traits that determine reproductive isolation evolve repeatedly, in closely related populations, as by-products of adaptation to ecological conditions. The outcome of such parallel evolution is that ecologically divergent pairs of populations exhibit greater levels of reproductive isolation than ecologically similar pairs of populations of a similar or younger age. The parallel evolution of reproductive isolation provides strong evidence for natural selection in the process of speciation, but only one conclusive example from nature is known. Populations of the walking-stick insect Timema cristinae that use different host-plant species have diverged in body size and shape, host preference, behaviour and the relative frequency of two highly cryptic colour-pattern morphs. Here we report that divergent selection for host adaptation, and not genetic drift, has promoted the parallel evolution of sexual isolation in this species. Our findings represent a clear demonstration that host-plant adaptation can play a crucial and repeatable role in the early stages of speciation.

Adaptation, Physiological↗

Resilience and variability in pathogens and hosts.

Adaptability by means of phenotype variability in host-pathogen systems is studied using a model that resembles a class of array systems known as cellular automata. Each automaton in this model is characterized by a network of n x m processors that process the information contained in levels 0 to m. The effect of the automaton's architecture on its ability to satisfy variations in constraints is analysed, and automata-evolution experiments are described. Increasing the number of organization levels in the automaton is shown to increase its efficiency in buffering external changes, and the mechanism of modulating the processing rules appears more efficient than the mechanism of controlling the mutation rate. Analogy with biological systems suggests that hosts and pathogens evolve towards increasing modulation of their genomic information processing and that single mature lymphocytes should be able to generate more than one antigen receptor. These hypotheses can provide an explanation for the sequential ordered expression of different antigen genes in trypanosomes, as well as for immunosuppression and autoimmune phenomena.

Animals↗

Divergent host plant adaptation and reproductive isolation between ecotypes of Timema cristinae walking sticks.

Theoretical and empirical studies have demonstrated that divergent natural selection can promote the evolution of reproductive isolation. Three unresolved questions concern the types of reproductive barriers involved, the role of geography, and the factors determining the extent of progress toward complete speciation. Here I synthesize studies of Timema cristinae host plant ecotypes to address these issues. The approach is to compare the magnitude of multiple reproductive barriers among different ecological and geographic scenarios, where pairs of populations within each scenario are the unit of replication. Application of this approach to T. cristinae revealed that divergent host adaptation can promote the evolution of diverse reproductive barriers, including those that are not inherently ecological. Gene flow in parapatry tended to constrain divergence, with the notable exception of the reinforcement of sexual isolation. Thus, geography affected progress toward speciation but did not influence all reproductive barriers in the same way. Studies of any single pair of taxa often capture only certain stages of the speciation process. For example, reproductive isolation between T. cristinae ecotypes is incomplete, and so only the stages before the completion of speciation have been examined. Studies of more divergent taxa within the genus are required to determine the factors that complete speciation.

Adaptation, Physiological↗

Host-plant adaptation in an herbivorous marine amphipod: genetic potential not realized in field populations.

Evolutionary responses of herbivores to their host plants depend not only on selection from plants, but also on the genetic basis of traits relating to host use. The genetic basis of such traits has been investigated extensively among terrestrial insect herbivores, but has received almost no attention among marine herbivores. We tested whether performance traits in the herbivorous marine amphipod Peramphithoe parmerong display heritable variation and, for the first time for a marine herbivore, whether selection has resulted in local adaptation to host plants on two spatial scales. Peramphithoe parmerong displayed heritable genetic variation for survival on two host macroalgae, the high-quality Sargassum linearifolium and the poor-quality Padina crassa, and for growth on S. linearifolium. Differences in performance on different hosts thus have the potential to select for differential use of hosts by this amphipod. Despite this potential, there was no evidence among field populations of local adaptation to host algae on either scale tested: between hosts within a site or among sites differing in algal species composition. Within a site, amphipods were not more likely to prefer or perform better on the host on which they were collected. Similarly, amphipods collected from sites in which P. crassa was present were not more likely to perform well on this host than amphipods collected from sites where this alga was not found. Ecological factors that may explain the persistence of P. parmerong on P. crassa and the possibility of phylogenetic constraints on host use by P. parmerong are discussed.

Adaptation, Physiological↗