Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Opinion TRENDS in Parasitology Vol.20 No.11 November 2004 The surface–mosaic model in host– parasite relationships J. Santiago Mejia1, Fernando Moreno2, Carlos Muskus3, Iván D. Vélez3 and Richard G. Titus1 1 Department of Microbiology, Immunology and Pathology, Colorado State University, Central receiving 200 W. Lake St. Campus Delivery 1619, CO 80523, USA 2 Instituto de Ciencias de la Salud (CES), Calle 10a No. 22–04, Medellı́n, Colombia 3 Programa de Estudio y Control de Enfermedades Tropicales (PECET), Universidad de Antioquia, Calle 62 No. 52–25, Medellı́n, Colombia The dynamics of protein adsorption to a microbial surface could be of significance in host–parasite relationships because non-defense proteins might interfere with the binding of defense proteins. A surface mosaic of defense and non-defense proteins formed on the microbial surface could activate one of the tissue reactivity programs via a binary code (help or silence) generated by the adsorbed proteins. Understanding the mechanisms of the mosaic formation and its evolution might help to identify evasion mechanisms used by virulent microorganisms. This also provides a conceptual framework to design new strategies to control the infectious diseases they cause. The nonspecific interaction between proteins and the surface of materials used in the manufacture of various medical devices (including implants, prosthesis, dialysis membranes and drug delivery systems) has been the focus of intense research in the field of biomedical engineering [1–4]. The analysis of plasma proteins adsorbed to the surface materials indicates that minor differences in charge density, hydrophobicity or surface-exposed functional groups account for significant changes in the profile of adsorbed proteins [3,4]. This is of great significance because it is clear that the nature of the adsorbed proteins have an effect on subsequent events around the coated surface [1,5]. The information generated about how the body isolates, rejects or integrates an artificial material could provide clues into similar events that occur when the body is exposed to the surface of a microorganism. This review describes a model that addresses the potential significance of protein adsorption to the surface of microorganisms in the early phase of host–parasite relationships. The adsorption process The adsorption of proteins to a surface is a complex process driven by the free energy generated at the liquid– solid interface and is characterized by a fast initial phase of adsorption (seconds) followed by a slower one that tends to saturate the surface until an equilibrium is reached [6]. Corresponding author: J. Santiago Mejia ([email protected]). Available online 26 August 2004 Different forces are at play during this process, including: (i) the affinity of the proteins for the surface; (ii) the intermolecular attractions and repulsion forces of proteins; (iii) the lateral diffusion of the adsorbed proteins; and (iv) the conformational modification that the proteins could undergo upon adsorption [7–10]. Several physicochemical characteristics of a surface (i.e. hydrophobicity, electrical charge, chemical reactivity and topology) have an effect on the adsorption process. Of these, the degree of hydrophobicity seems to be the major determinant of both the amount and type of proteins that are adsorbed [3,4,10] due in part to the higher degree of free energy generated at the interface. Accordingly, covering surfaces with amphiphilic molecules has been shown to reduce significantly the amount of proteins adsorbed to the surface [11]. When the surface is in contact with body fluids, a complex protein layer or mosaic forms at the interface. Considering the diversity of proteins present in a tissue, that each one of them might adsorb to a surface via different domains and that there could be different degrees of conformational modification of the protein structure upon adsorption, the mosaic must be a structure of extraordinary complexity. Furthermore, the mosaic could evolve as a result of protein exchange (Vroman effect), a phenomenon whereby initially adsorbed proteins can desorb to be replaced by other proteins with stronger attractive interaction for the surface [12]. Defense and non-defense proteins Any host protein can be part of a mosaic as long as it has access to the exposed surface and is able to compete with other proteins, especially those present at the highest concentrations in tissues. This has been extensively studied with plasma proteins, where the dominant role played by the most abundant proteins (albumin, fibrinogen, immunoglobulins and lipoproteins) has been demonstrated [3,4]. Some of the plasma proteins are members of defense systems (e.g. complement, coagulation and immune), whereas others are members of non-defense systems in charge of transporting, for example, lipids, hormones, vitamins and metals (albumin, lipoproteins and transferrin). This functional separation is crucial because nondefense proteins could interfere with the binding of defense www.sciencedirect.com 1471-4922/$ - see front matter Q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.pt.2004.08.005 Opinion TRENDS in Parasitology proteins, making the ratio of defense to non-defense proteins (DND ratio) an important element in the outcome of the interaction between a surface and a particular tissue compartment (intracellular, extracellular or mucosal). The code The competitive nature of protein adsorption to a surface provides a scenario in which non-defense proteins generate a silence code on the surface, isolating it from the defense systems and minimizing the tissue reactivity against it. However, by providing a help code, the defense proteins can focus the activation of the defense systems (contact, coagulation, complement, immune and vascular) on the surface. The surface–mosaic model There has been a great deal of discussion as to whether the initial events in host–parasite relationships involve danger signals generated by the tissues, or recognition of molecular patterns present on the microorganism [13–15]. One problem with these models is that they have neglected the participation of the non-defense proteins that are abundantly expressed in every tissue compartment. We postulate that defense and non-defense proteins compete for binding to the injury-associated surface. The spatial and temporal character of the binary code (help or silence) generated by the defense and non-defense proteins, respectively, defines the main tissue reactivity programs (isolation, containment, rejection or integration) that are triggered around the surface (Figure 1). The significance of this feature in a host–parasite relationship is that non-defense proteins might interfere with the recognition of the microorganism by the innate or adaptive defense mechanisms of the body, in effect generating a period during which isolation and not recognition could be the initial outcome of the interaction. Implications of the surface–mosaic model The DND ratio as a modulator of the mosaic composition In a healthy non-injured organism, the DND ratio of the main tissue compartments (mucosal, intracellular and extracellular) can be anticipated to be set in a silence mode (low DND ratio) and that a shift towards a proinflammatory mode (high DND ratio) occurs as a response to an injury. This shift occurs because several events take place: (i) an increase in vascular permeability allows high molecular weight proteins of the proinflammatory systems to leak into the extracellular fluid [16]; (ii) the activation of cells at the injury site induces the production of cytokines that in turn promote the expression of various defense genes [17]; and (iii) during the systemic acute phase reaction concurrent with the increase in synthesis of defense proteins, there is a decrease in some of the most abundant non-defense plasma proteins (albumin and transferrin) [18]. The mosaic as a danger-sensing structure Defining the degree of danger associated with a suddenly exposed surface during an injury is central to tissue homeostasis because an excessive response is as detrimental in evolutionary fitness as the lack of a response. When an injury-associated surface is exposed to an environment www.sciencedirect.com Vol.20 No.11 November 2004 509 with a low DND ratio, the main tissue reactivity program is isolation. However, if the mostly non-defense mosaic is modified by proteases associated with the underlying surface, danger signals (peptides) might diffuse into the surrounding tissues, thus changing the character of the tissue reactivity program. In this regard, the surface mosaic could behave as a proteolysis sensor and thus represent an additional system for pathogen sensing [19]. The orientation paradox Because the code generated by a defense protein upon adsorption to a surface might depend on the appropriate orientation towards the triggering surface, the defense protein might behave as a non-defense protein if it adsorbs to a surface with the inappropriate orientation. This possibility seems to operate with immunoglobulins in that they are able to adsorb to a variety of artificial materials in a process that is not dependent on the specificity of the antigen-binding site [3,4]. This non-specific interaction of immunoglobulins with surfaces could provide an alternative explanation to the anti-inflammatory effect that preparations of human immunoglobulins have in a variety DND ratio Low High Intermediate Mosaicforming proteins Mosaic Parasite surface Tissue reactivity programs Isolation, containment, rejection and integration Help Silence Code TRENDS in Parasitology Figure 1. Elements of the surface-mosaic model. (i) The ratio of defense to nondefense proteins (DND ratio); (ii) pool of mosaic-forming proteins; (iii) mosaic; (iv) parasite surface; (v) code and (vi) tissue reactivity programs. The adsorption of defense proteins (red) or non-defense proteins (blue) to the surface of a parasite might generate a protein mosaic that conveys the code (help or silence) required to implement one of the tissue reactivity programs. Each tissue compartment: mucosal (squares), extracellular (spheres) or intracellular (cylinders) have a particular DND ratio. In those compartments with low DND ratio, the abundant non-defense proteins generate a silence code that isolates the surface. When the limits between compartments is ruptured, as frequently occurs in an injury, a code conflict might ensue because of two events: (i) elements of the mosaic generated in one compartment might remain in a different compartment providing an inadequate code; and (ii) the sudden influx of proteins from one compartment into another shifts the DND ratio modifying its coding potential. The ability of some microorganisms to recruit mosaics rich in non-defense proteins or modify the local DND ratio might represent a general mechanism of evasion of the host defense mechanisms. 510 Opinion TRENDS in Parasitology of human inflammatory diseases [20]. The abundance of receptors for a variety of host proteins (defense and nondefense) in virulent microorganisms [21,22] emphasizes the significance of this evasion mechanism in host– parasite relationships. The dilemma of isolation versus recognition The ability of mucins to isolate surfaces (microbial and otherwise) is one of the main defense mechanisms at mucosal surfaces [23,24], and is very effective as long as the covered surface remains in the luminal side of the mucosa. The silence code conveyed by the mucins when a mucin-covered microorganism reaches the underlying tissues could represent an important evasion mechanism in the immunobiology of microorganisms that first colonize mucosal surfaces before invading and disseminating [25,26]. In order to invade the tissues, the virulent microorganism implements one of a variety of mechanisms to breach the structural elements (plasma membranes and cytoskeletons) which define the compartments. A code conflict might be generated by such disruption because each compartment has different DND ratios. When cells with a very high concentration of non-defense proteins, such as hemoglobin-rich erythrocytes, are ruptured, the extracellular DND ratio is suddenly shifted toward a silence code, a phenomena that might explain why the expression of hemolysins is associated with virulence [27]. Role of the surface mosaic in defense evasion mechanisms of virulent microorganisms The expression of receptors for non-defense proteins such as albumin [28,29], Hb [30] or lipoproteins [31] by virulent microorganisms could represent an evasion mechanism because they tend to recruit a mosaic enriched in nondefense proteins. The expression of hydrophobic surfaces, as has been shown in virulent bacteria [32], fungi [33] and helminths [34], might represent a similar evasion mechanism because some of the most abundant nondefense proteins (albumin, lipoproteins) have affinity for hydrophobic compounds. For all of these microorganisms, the stability of the surface mosaic is anticipated to be crucial because the surface mosaic tends to perpetuate isolation from host defenses. However, a stable surfacemosaic might interfere with molecular interactions that are essential for the survival of some microorganisms with complex life cycles such as Leishmania, Plasmodium or Schistosoma. Perhaps the expression of amphiphilic compounds [35–37] or proteases [38,39] on the surface of some of these parasites represent mechanisms to minimize the potential isolating effect of the surface mosaic. In some of the most complex parasites, such as Plasmodium sporozoites [40] or adult stages of Schistosoma japonicum [41], the same effect might be accomplished with a complex mechanism of surface renewal. The mosaic as a potential target of protective immunity The pathogens transmitted by hematophagous arthropods represent a special group of diseases because proteins from the invertebrate host might form a mosaic on the surface of the infective stages of the microorganism, thus raising two important considerations for the www.sciencedirect.com Vol.20 No.11 November 2004 immunobiology of these diseases: (i) the invertebrate mosaic might initially interfere with recognition of the parasite by the vertebrate host immune system; and (ii) the invertebrate mosaic itself might be a target of protective immunity against these microorganisms. The saliva of hematophagous arthropods has been shown to interfere with the functionality of many defense systems of the vertebrate hosts [42–44], and to increase the infectivity of several microorganisms [45–48]. Accordingly, neutralization of the disease-promoting molecules present in arthropod saliva is now being used as an approach to develop vaccines against arthropod-borne diseases [49,50]. It remains to be studied which salivary components tend to adsorb to the surface of these microorganisms because they could represent yet another target for the development of vaccines against diseases such as malaria, leishmaniasis, Lyme borreliosis or dengue fever. Concluding remarks The role that non-defense proteins play in the biology of artificial surface rejection or integration has been studied extensively. It is necessary to examine whether they play a similar biological role in host–parasite relationships because it might help our understanding of the evasion mechanisms used by virulent microorganisms in their interaction with vertebrate and invertebrate hosts. This might also provide a conceptual framework to design new strategies to control the infectious diseases they cause. Acknowledgements We are grateful to Carolina Barillas-Mury, Sara Robledo and Juan F. Alzate for helpful suggestions, and to Barry J. Beaty, Stephen M. Beverley, Salvatore J. Turco, Jose M. Ribeiro, Clotilde K. Carlow, William C. Black IV, Francisco J. Diaz, Jeannette V. Bishop, Keith Nelson, Gustavo G. Carrio and Juan F. Granada for critical review of the manuscript. In addition, J.S.M. acknowledges Claudia Bernal. This work was supported by funds from: Instituto de Ciencias de la Salud; Programa de Estudio y Control de Enfermedaded Tropicales; Universidad de Antioquia; and by National Institutes of Health grant no. AI27511. References 1 Klee, D. and Hocker, H. (1999) Polymers for biomedical applications: improvement of the interface compatibility. Adv. Polym. Sci. 149, 1–57 2 Chanard, J. et al. (2003) New insights in dialysis membrane biocompatibility: relevance of adsorption properties and heparin binding. Nephrol. Dial. Transplant. 18, 252–257 3 Luck, M. et al. (1998) Analysis of plasma protein adsorption on polymeric nanoparticles with different surface characteristics. J. Biomed. Mater. Res. 39, 478–485 4 Gessner, A. et al. (2003) Functional groups on polystyrene model nanoparticles: Influence on protein adsorption. J. Biomed. Mater. Res. 65A, 319–326 5 Tang, L. et al. (1996) Molecular determinants of acute inflammatory responses to biomaterials. J. Clin. Invest. 97, 1329–1334 6 Fang, F. and Szleifer, I. (2001) Kinetics and thermodynamics of protein adsorption: a generalized molecular theoretical approach. Biophys. J. 80, 2568–2589 7 Ravichandran, S. and Talbot, J. (2000) Mobility of Adsorbed Proteins: A Brownian Dynamics Study. Biophys. J. 78, 110–120 8 Minton, A.P. (2000) Effects of excluded surface area and adsorbate clustering on surface adsorption of proteins I. Equilibrium models. Biophys. Chem. 86, 239–247 9 Brash, J.L. and Horbett, T.A. (1995) Proteins at interphases. An overview. In Proteins at Interfaces II: Fundamentals and Applications (Horbett, T.A. and Brash, J.L. eds), pp. 1–23, American Chemical Society 10 Kim, J. and Somorjai, G.A. (2003) Molecular packing of lysozyme, Opinion 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 TRENDS in Parasitology Vol.20 No.11 November 2004 fibrinogen, and bovine serum albumin on hydrophilic and hydrophobic surfaces studied by infrared-visible sum frequency generation and fluorescence microscopy. J. Am. Chem. Soc. 125, 3150–3158 Ishihara, K. et al. (1998) Why do phospholipid polymers reduce protein adsorption? J. Biomed. Mater. Res. 39, 323–330 Slack, S.M. and Horbett, T.A. (1995) Vroman effect: a critical review. In Proteins at Interfaces II: Fundamentals and Applications (Horbett, T.A. and Brash, J.L. eds), pp. 112–127, American Chemical Society Matzinger, P. (2002) The Danger Model: a renewed sense of self. Science 296, 301–305 Janeway, C.A., Jr. (2001) How the immune system works to protect the host from infection: A personal view. Proc. Natl. Acad. Sci. U. S. A. 98, 7461–7468 Vance, R.E. (2000) Cutting edge commentary: a copernican revolution? Doubts about the danger theory. J. Immunol. 165, 1725–1728 Michel, C.C. and Curry, F.E. (1999) Microvascular permeability. Physiol. Rev. 79, 703–761 Kisseleva, T. et al. (2002) Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 285, 1–24 Gabay, C. and Kushner, I. (1999) Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 340, 448–454 Pulendran, B. et al. (2001) Sensing pathogens and tuning immune responses. Science 293, 253–256 Kazatchkine, M.D. and Kaveri, S.V. (2001) Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N. Engl. J. Med. 345, 747–755 Talay, S.R. et al. (1996) Structure of a group C streptococcal protein that binds to fibrinogen, albumin and immunoglobulin G via overlapping modules. Biochem. J. 315, 577–582 Kronvall, G. and Jonsson, K. (1999) Receptins: a novel term for an expanding spectrum of natural and engineered microbial proteins with binding properties for mammalian proteins. J. Mol. Recognit. 12, 38–44 Van Klinken, B.J. et al. (1995) Mucin gene structure and expression: protection vs. adhesion. Am. J. Physiol. 269, G613–G627 Shi, L. and Caldwell, K.D. (2000) Mucin adsorption to hydrophobic surfaces. J. Colloid Interface Sci. 224, 372–381 Hicks, S.J. et al. (2000) The role of mucins in host-parasite interactions. Part I – Protozoan parasites. Parasitol. Today 16, 476–481 Theodoropoulos, G. et al. (2001) The role of mucins in host-parasite interactions: Part II – Helminth parasites. Trends Parasitol. 17, 130–135 Nizet, V. (2002) Streptococcal beta-hemolysins: genetics and role in disease pathogenesis. Trends Microbiol. 10, 575–580 de Château, M. et al. (1996) Protein PAB, an albumin-binding bacterial surface protein promoting growth and virulence. J. Biol. Chem. 271, 26609–26615 Johansson, M.U. et al. (2002) Structure, specificity, and mode of interaction for bacterial albumin-binding modules. J. Biol. Chem. 277, 8114–8120 Jin, H. et al. (1999) Characterization of hgpA, a gene encoding a haemoglobin/haemoglobin- haptoglobin-binding protein of Haemophilus influenzae. Microbiology 145, 905–914 Tempone, A.J. et al. (1997) The interaction of human LDL with the tegument of adult Schistosoma mansoni. Mol. Cell. Biochem. 177, 139–144 511 32 Doyle, R.J. (2000) Contribution of the hydrophobic effect to microbial infection. Microbes Infect. 2, 391–400 33 Singleton, D.R. et al. (2001) Cloning and analysis of a Candida albicans gene that affects cell surface hydrophobicity. J. Bacteriol. 183, 3582–3588 34 Redman, C.A. and Kusel, J.R. (1996) Distribution and biophysical properties of fluorescent lipids on the surface of adult Schistosoma mansoni. Parasitology 113, 137–143 35 Lochnit, G. et al. (2000) Phosphorylcholine substituents in nematodes: structures, occurrence and biological implications. Biol. Chem. 381, 839–847 36 Serino, L. and Virji, M. (2000) Phosphorylcholine decoration of lipopolysaccharide differentiates commensal Neisseriae from pathogenic strains: identification of licA-type genes in commensal Neisseriae. Mol. Microbiol. 35, 1550–1559 37 Turco, S.J. et al. (2001) Is lipophosphoglycan a virulence factor? A surprising diversity between Leishmania species. Trends Parasitol. 17, 223–226 38 Yao, C. et al. (2003) The major surface protease (MSP or GP63) of Leishmania sp. Biosynthesis, regulation of expression, and function. Mol. Biochem. Parasitol. 132, 1–16 39 Ghendler, Y. et al. (1996) Schistosoma mansoni: evidence for a 28-kDa membrane-anchored protease on schistosomula. Exp. Parasitol. 83, 73–82 40 Menard, R. (2001) Gliding motility and cell invasion by Apicomplexa: insights from the Plasmodium sporozoite. Cell. Microbiol. 3, 63–73 41 Gobert, G.N. et al. (2003) The ultrastructural architecture of the adult Schistosoma japonicum tegument. Int. J. Parasitol. 33, 1561–1575 42 Titus, R.G. and Ribeiro, J.M.C. (1990) The role of vector saliva in transmission of arthropod-borne diseases. Parasitol. Today 6, 157–160 43 Gillespie, R.D. et al. (2000) The immunomodulatory factors of bloodfeeding arthropod saliva. Parasite Immunol. 22, 319–331 44 Valenzuela, J.G. et al. (2003) Exploring the salivary gland transcriptome and proteome of the Anopheles stephensi mosquito. Insect Biochem. Mol. Biol. 33, 717–732 45 Titus, R.G. and Ribeiro, J.M. (1988) Salivary gland lysates from the sand fly Lutzomyia longipalpis enhance Leishmania infectivity. Science 239, 1306–1308 46 Mbow, M.L. et al. (1998) Phlebotomus papatasi sand fly salivary gland lysate down-regulates a Th1, but up-regulates a Th2, response in mice infected with Leishmania major. J. Immunol. 161, 5571–5577 47 Belkaid, Y. et al. (1998) Development of a natural model of cutaneous leishmaniasis: powerful effects of vector saliva and saliva preexposure on the long-term outcome of Leishmania major infection in the mouse ear dermis. J. Exp. Med. 188, 1941–1953 48 Edwards, J.F. et al. (1998) Mosquito feeding-induced enhancement of Cache Valley Virus (Bunyaviridae) infection in mice. J. Med. Entomol. 35, 261–265 49 Morris, R.V. et al. (2001) Sandfly maxadilan exacerbates infection with Leishmania major and vaccinating against it protects against L. major infection. J. Immunol. 167, 5226–5230 50 Valenzuela, J.G. et al. (2001) Toward a defined anti-Leishmania vaccine targeting vector antigens: characterization of a protective salivary protein. J. Exp. Med. 194, 331–342 The Innate Immune Response to Infection Edited by S.H.E. Kaufmann, R. Medzhitov and S. Gordon ASM Press, 2004, US$115.95 (hbk) (482 pages) ISBN: 1555812910 The Innate Immune Response to Infection delivers a timely, state-of-the-art review of the innate immune system, using the most current concepts of cellular and molecular biology. Unique in its presentation, this new volume covers all aspects of innate immunity with an emphasis on response to infectious agents. It is a valuable reference source for scientists and students active in all areas of immunology and microbiology, as well as virology, parasitology and infectious diseases. Written by experts in the field, the book focuses on evolutionary aspects, describing the major cells, humoral factors, and effector responses central to innate immunity and its important relation to acquired immunity. In-depth treatment is given to the performance of the innate immune system in various situations, including bacterial, viral, fungal and parasitic infection. For more information, please go to http://www.asmpress.org/ Compiled by Anthony Li ([email protected]) www.sciencedirect.com