Host-Parasitic Relationships among Human Protozoa
Molecular basis of host-parasite relationship: towards the definition of protective our understanding of the immune response to parasites and in the molecular cloning Helminth; Antigens, Protozoan; Host-Parasite Interactions/immunology *. Commensualism is defined as "eating at the same table". A dead host is usually not of use to the parasite, although death of the intermediate host may in some. Protozoa are eukaryotic organisms (with a membrane-bound nucleus) which To move from host-to-host, protozoan parasites use one of four main modes of.
This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Parasitic protozoa are among the most important pathogens worldwide. Diseases such as malaria, leishmaniasis, amoebiasis, giardiasis, trichomoniasis, and trypanosomiasis affect millions of people. Humans are constantly threatened by infections caused by these pathogens.
Parasites engage a plethora of surface and secreted molecules to attach to and enter mammalian cells. The secretion of lytic enzymes by parasites into host organs mediates critical interactions because of the invasion and destruction of interstitial tissues, enabling parasite migration to other sites within the hosts.
Extracellular matrix is a complex, cross-linked structure that holds cells together in an organized assembly and that forms the basement membrane lining basal lamina.
The extracellular matrix represents a major barrier to parasites. Therefore, the evolution of mechanisms for connective-tissue degradation may be of great importance for parasite survival. Recent advances have been achieved in our understanding of the biochemistry and molecular biology of proteases from parasitic protozoa.
The focus of this paper is to discuss the role of protozoan parasitic proteases in the degradation of host ECM proteins and the participation of these molecules as virulence factors. We divide the paper into two sections, extracellular and intracellular protozoa. Introduction The extracellular matrix ECM is the noncellular component present within all tissues and organs; it is produced mainly by a heterogeneous population of fibroblasts [ 1 ] and provides essential physical scaffolding for the cellular constituents as well as biochemical cues that are required for tissue morphogenesis, differentiation, and homeostasis.
The ECM is composed of water, proteins, and polysaccharides; each tissue has an ECM with a unique and different composition and a distinct topology.
Molecular basis of host-parasite relationship: towards the definition of protective antigens.
Cell adhesion to the ECM is tissue specific and is mediated by ECM receptors, such as integrins, discoidin domain receptors, and syndecans.
The ECM includes the interstitial matrix and the basement membrane, of which the interstitial matrix is present between cells, whereas the basement membrane is a thin, sheet-like deposition of ECM that surrounds cells e. The basement membrane is composed of two layers: Adhesion mediates cytoskeletal coupling to the ECM and is involved in cell migration; the ECM is also a highly dynamic structure that is constantly being remodeled, both enzymatically and nonenzymatically, and its molecular components are subjected to various types and numbers of posttranslational modifications [ 4 ].
The ECM is composed of two main classes of macromolecules: PGs are composed of glycosaminoglycan GAG chains covalently linked to a specific protein core. PGs have been classified based on their core protein localization and GAG composition. The three main families are small leucine-rich proteoglycans SLRPsmodular proteoglycans, and cell surface proteoglycans [ 5 ]. PGs occupy the majority of extracellular interstitial space within the tissue in the form of a hydrated gel [ 6 ].
PGs have a wide variety of functions that reflect their unique buffering, hydration, binding, and force-resistance properties. The main fibrous ECM proteins are collagens, elastins, fibronectins, and laminin. This protein constitutes the main structural element of connective tissues and also provides tensile strength, regulates cell adhesion, supports chemotaxis and migration, and directs tissue development [ 7 ].
Collagen associates with elastin, another major ECM fiber. Elastin provides recoil to tissues that undergo repeated stretch. A third fibrous protein, fibronectin FNis intimately involved in directing the organization of the interstitial ECM and also plays a crucial role in mediating cell attachment and function [ 8 ]. Additionally, FN is important for cell migration during development and has been implicated in cardiovascular disease and tumor metastasis [ 7 ].
Laminins and collagen type IV form independent networks that are connected by nidogen and perlecan [ 9 ]. Host-Parasite Relation Every mammalian host is in constant danger of infection caused by pathogens, such as viruses, bacteria, fungi or parasites.
Host defense against these pathogens requires a well-regulated inflammatory response marked by leukocyte migration into the site of infection, destruction of the microorganisms, resolution of inflammation, and, finally, healing and repair of the tissue architecture. Generally speaking, the relationship between host and parasite determines the outcome of the infection.
Indeed, on an evolutionary scale, most parasites have developed adaptive mechanisms to evade host immune system responses. Many of these molecules are involved in triggering specific signaling pathways, both in the parasite and the host cell, that are critical for parasite entry and survival.
Several important advances have been achieved in identifying factors that are critical to parasite virulence and the pathogenesis of the diseases they cause. Among the most widely studied of these factors are parasite-derived proteases. Parasitic proteases can play a variety of roles in establishing, maintaining, and exacerbating an infection. Most of the human protozoan parasites invade, migrate, and reside within a variety of tissues and organs, whether they are intracellular or extracellular parasites.
Interestingly for some parasites it has recently been reported the induction of ECM proteases in host cells. Connective tissue and basement membranes represent major barriers to parasite invasion, dissemination, and access to essential nutrients. Thus, mechanisms for connective tissue degradation might be critical for parasite survival.
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Therefore, we divide the paper into two sections discussing extracellular and intracellular protozoa. Parasite cysts are transmitted through contaminated food and water. Parasite excystation in the small intestine produces eight trophozoites per cyst, which then colonize the large intestine [ 11 ]. Parasite destruction of host cells appears to be the basis of disease; invasive disease pathologies, such as colitis and liver abscesses, are associated with tissue invasion and massive host tissue destruction [ 12 ].
For example, flask-shaped ulcers, a hallmark of amoebic colitis, is characterized by severe damage to enteric cells as well as the migration to the lamina propria and blood vessels [ 13 ]. It has been proposed that for the initial contact or adhesion, surface carbohydrates on the target cell are recognized by specific molecules lectins. Other proteins also contribute to host cell binding on target cells [ 14 ]. Once the targets are partially digested, the amoeba internalizes the cell debris and substrate fragments by phagocytosis [ 18 ].
In contrast, the interaction of trophozoites with extracellular matrix ECM components results in the proteolysis and destruction of the connective tissue [ 19 ]. These proteases have been demonstrated to act on a variety of host substrates in vitro [ 21 — 25 ]. At least some of these proteases are secreted, and a few have been characterized as surface localized; hence, they have the potential to contribute to host tissue breakdown in vivo. An in vitro model was developed to analyze the interaction of E.
The assays quantitatively monitored the adhesion of trophozoites to purified FN-covered surfaces and the breakdown of this protein under diverse experimental conditions. The data showed specificity in the binding and the occurrence of structural and biochemical events in the amoebas that participate in and promote the adhesion to the substrate and the later degradation. Similar results were obtained with laminin and Matrigel.
A putative amoebic fibronectin receptor with a molecular weight of 37 kDa was found [ 2728 ]. The adhesion to fibronectin triggers proteolytic enzyme release, which facilitates the local degradation of the substrate [ 272830 ].
Certain of these secreted proteases show similarities to cathepsin B [ 17 ] and might generate fragments with chemotactic and chemokinetic properties that are able to promote binding as well as locomotion of trophozoites [ 31 ]. Collagen is a major component of the basal lamina and the ECM components of the intestine. There are three collagen-binding proteins described in E.
Antibodies raised against the 30 kDa molecule inhibit the binding of trophozoites to collagen [ 32 ]. Several of the proteolytic activities related with ECM degradation are summarized in Table 1 and Figure 1.
Extracellular parasite-derived proteases that degrade human ECM proteins. The collagenase was more active against type I collagen. Three major fragments of 75, 50, and 25 kDa were obtained from collagen type I when this protein was incubated with E. After this incubation period, smaller fragments of collagen were found, possibly due to the action of other proteolytic enzymes. The collagenase activity was found mainly in electron-dense granules in E. These granules were induced and secreted in response to the incubation of collagen type I with trophozoites of E.
In another study, one specific collagenase activity with a molecular weight of 72 kDa was found in E.
- Host-Parasitic Relationships among Human Protozoa
- HOST-PARASITE RELATIONSHIPS OF CERTAIN INTESTINAL PROTOZOA IMPORTANT TO MEDICAL ZOOLOGY
- Journal of Parasitology Research
This activity was found in electron-dense granules and could be related to the actin cytoskeleton function because one cytoskeleton-altered amoeba BG-3 derived from the pathogenic HM1-IMSS strain had less collagenase activity [ 33 ].
There is evidence supporting the role of the extracellular cysteine proteases of E. CP purified from axenized E.
CP-A5 and CP-B9 cysteine proteases possess gelatinase activity in vitro [ 3436 ] and may have a role during tissue invasion. In a recent work [ 37 ] using 3D collagen matrix determined that amoebic CPs are responsible for the collagenase activity and that these enzymes have an important role during cell migration through a three-dimensional collagen scaffold.
In this work, the authors also hypothesize that CP5 promotes inflammation and the secretion of host metalloproteases MMP that contribute to the ECM destruction.
Finally, the collagenolytic activity of E. In all the studies, the more virulent strain always has the higher collagenolytic activity. The study of E. The trophozoite is the disease-causing stage of the parasite [ 69 ]. An estimated million people have symptomatic giardiasis worldwide, and children under 5 years are at particular risk [ 70 ]. These alterations conduct to diarrhea and malabsorption syndrome [ 7172 ]. Adhesion to ECM could be important for colonization, since trophozoite attachment was demonstrated to be even more effective to type I collagen than to the apical surface of confluent Madin Darby canine kidney MDCK cells in vitro [ 73 ].
Giardia releases products that may contribute to pathogenesis, such as proteases, although they have not been well characterized yet [ 7475 ]. Little information is available regarding specific proteins against ECM. There are only three reports regarding the collagenolytic activity using zymograms Table 1Figure 1.
Williams and Coombs [ 76 ] explored intracellular proteases present in lysates of trophozoites and observed collagen degradation by a group of low molecular mass proteases 30—65 kDaplus one of kDa [ 76 ]. Differences on the hydrolysis patterns were observed in relation to the Giardia trophozoite strain [ 38 ]. The significance of these differences in the enzymatic activity remains to be determined, and it would be interesting to identify if it correlates with strain virulence.
Additional research is required to confirm this hypothesis, from the identification of the genes encoding for these collagenases to the use of animal models to test their contribution to the infection.
Acanthamoeba is a free-living amoeba and is an opportunistic protozoan parasite. It is ubiquitously distributed throughout the environment. More than 30 cases of Acanthamoeba keratitis were identified recently from the Chicago Illinois area alone. It is estimated that as of August more than cases of Acanthamoeba keratitis have occurred in the United States. Because Acanthamoeba keratitis is not a reportable disease in the United States, the actual number is not known and may be even higher.
Large numbers of cases have also been reported from the United Kingdom and India [ 77 ]. The name of this protozoan comes from the presence of spine-like structures on its surface. This amoeba has a simple life cycle with two stages, a vegetative stage, or trophozoite, and a resistant stage, or cyst.
Parasite adhesion to target cells or tissues is a necessary step to invade the host; this step is mediated by a kDa mannose-binding protein MBPwhich is a surface-expressed protein [ 78 ].
Other adhesins include a laminin-binding protein of In these interactions, amoebas exhibit a stronger attachment to the basal membrane components laminin and collagen IV.
The adhesion to these molecules leads to secondary responses, such as phagocytosis and toxin production, that result in host cell death via the phosphatidylinositol 3-kinase PI3K pathway [ 83 ]. Additionally, Acanthamoeba has been shown to display plasminogen activator activity, which can trigger host MMP leading to the degradation of basement membranes.
Acanthamoeba also possesses hydrolytic enzymes, such as elastases [ 84 ], phospholipases [ 85 ], serine proteases [ 86 — 89 ], CP [ 8689 ], and contact metalloproteases [ 90 ]. There are many proteases in Acanthamoeba that are able to degrade certain components of ECM proteins Table 1Figure 1.
Collagen is one of the major components of the cornea, so keratitis is directly linked to the collagenolytic activity. More importantly, in vivo studies demonstrated the pathogenic features of this parasite product, as A. The use of nonspecific protease inhibitors and ethylenediaminetetraacetic acid-Na EDTA-Na with Acanthamoeba-conditioned medium completely blocked the degradation of collagen shields, and the use of EDTA-Na in vivo also blocked amoebic collagenase activity.
They concluded that A. The purified protease had a molecular weight of 33 kDa, a pH optimum of 8. This protease degrades collagens type I and IV and fibronectin. This molecule was a chymotrypsin-like serine protease that could degrade various protein substrates, such as collagen, fibronectin, laminin, secretory IgA, IgG, plasminogen, fibrinogen, hemoglobin, and rabbit corneal protein. The researchers also used the purified protein to test cytopathogenicity toward HEp2 cells, which resulted in the loss of viability within 12 h.
The cytopathogenic events were completely inhibited when the protease was pre-treated with PMSF before being added to the HEp2 cells. The purified 33 kDa protease had a pH optimum of 8. The use of PMSF inhibited almost all of the protease activity. Furthermore, Kim et al. The kDa protease was inhibited by PMSF, suggesting that it is a serine protease, whereas the kDa protease was inhibited by 1, phenanthroline, suggesting that it is a metalloprotease.
Both proteases exhibited maximal activity at neutral pH and over a range of temperatures. These activities are in the range of 70— kDa, and they have an optimal pH of 7.
This study demonstrates that amoebic trophozoites secrete elastase activities and suggests the high-molecular-weight serine proteases as possible elastase candidates. Finally, de Souza Carvalho et al.
Different enzymatic patterns of collagenases were observed, varying between single and multiple collagenase activities. Low-molecular-weight serine proteases were secreted by the trophozoites and were associated with a more severe clinical course of the keratitis. Consequently, Acanthamoeba proteolytic enzymes could be related to the degree of virulence and clinical manifestations of disease in human keratitis. More studies are necessary to comprehend the importance of the proteases of this parasite in the diseases caused by Acanthamoeba spp.
A virus is an obligate parasite, acting as a living thing only to the extent that when it is in a host cellthe machinery of that cell makes copies of the virus. A single reservoir host may be reinfected several times.
For trypanosomesthe cause of sleeping sicknessstrictly, humans are the secondary host, while the tsetse fly is the primary host, given that it has been shown that reproduction occurs in the insect. It is not always easy or even possible to identify which host is definitive and which secondary. As the life cycles of many parasites are not well understood, sometimes the subjectively more important organism is arbitrarily labelled as definitive, and this designation may continue even after it is found to be incorrect.
For example, sludge worms are sometimes considered "intermediate hosts" for salmonid whirling diseaseeven though the myxosporean parasite reproduces sexually inside them. Paratenic hosts serve as "dumps" for non-mature stages of a parasite in which they can accumulate in high numbers. The trematode Alaria americana may serve as an example: The tadpoles are more frequently preyed on by snakesin which the mesocercariae may not undergo further development.
However, the parasites may accumulate in the snake paratenic host and infect the definitive host once the snake is consumed by a canid. For example, humans and horses are dead-end hosts for West Nile viruswhose life-cycle is normally between culicine mosquitoes and birds.
This can be wide or narrow, but it never includes all plants.
Molecular basis of host-parasite relationship: towards the definition of protective antigens.
Occurrence of a disease in a population over a defined period of time. When bacteria are actually growing and dividing in the blood. Commonly felt by the patient. Commonly observed by a physician. Nosocomial infections -- Hospital acquired infections are especially fearsome because: The incubation period - initial infection and the first appearance of signs or symptoms. The prodromal period -short duration. Period of initial mild sign or symptoms.
The period of illness -period of maximum presentation of signs and symptoms. The period of decline -signs and symptoms start to decline. Carrier human -- Inapparent infections, subclinical infection, chronic infection.