In vitro maturation of Toxoplasma gondii bradyzoites in human myotubes and their metabolomic characterization.

The apicomplexan parasite Toxoplasma gondii forms bradyzoite-containing tissue cysts that cause chronic and drug-tolerant infections. However, current in vitro models do not allow long-term culture of these cysts to maturity. Here, we developed a human myotube-based in vitro culture model of functionally mature tissue cysts that are orally infectious to mice and tolerate exposure to a range of antibiotics and temperature stresses. Metabolomic characterization of purified cysts reveals global changes that comprise increased levels of amino acids and decreased abundance of nucleobase- and tricarboxylic acid cycle-associated metabolites. In contrast to fast replicating tachyzoite forms of T. gondii these tissue cysts tolerate exposure to the aconitase inhibitor sodium fluoroacetate. Direct access to persistent stages of T. gondii under defined cell culture conditions will be essential for the dissection of functionally important host-parasite interactions and drug evasion mechanisms. It will also facilitate the identification of new strategies for therapeutic intervention.

Comparative multi-omics analyses reveal differential expression of key genes relevant for parasitism between non-encapsulated and encapsulated Trichinella.

Genome assemblies provide a powerful basis of comparative multi-omics analyses that offer insight into parasite pathogenicity, host-parasite interactions, and invasion biology. As a unique intracellular nematode, Trichinella consists of two clades, encapsulated and non-encapsulated. Genomic correlation of the distinct differences between the two clades is still unclear. Here, we report an annotated draft reference genome of non-encapsulated Trichinella, T. pseudospiralis, and perform comparative multi-omics analyses with encapsulated T. spiralis. Genome and methylome analyses indicate that, during Trichinella evolution, the two clades of Trichinella exhibit differential expansion and methylation of parasitism-related multi-copy gene families, especially for the DNase II members of the phospholipase D superfamily and Glutathione S-transferases. Further, methylome and transcriptome analyses revealed divergent key excretory/secretory (E/S) genes between the two clades. Among these key E/S genes, TP12446 is significantly more expressed across three life stages in T. pseudospiralis. Overexpression of TP12446 in the mouse C2C12 skeletal muscle cell line could induce inhibition of myotube formation and differentiation, further indicating its key role in parasitism of T. pseudospiralis. This multi-omics study provides a foundation for further elucidation of the mechanism of nurse cell formation and immunoevasion, as well as the identification of pharmacological and diagnostic targets of trichinellosis.

The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice.

Mutations in the Des gene coding for the muscle-specific intermediate filament protein desmin lead to myopathies and cardiomyopathies. We previously generated a R349P desmin knock-in mouse strain as a patient-mimicking model for the corresponding most frequent human desmin mutation R350P. Since nothing is known about the age-dependent changes in the biomechanics of affected muscles, we investigated the passive and active biomechanics of small fiber bundles from young (17-23 wks), adult (25-45 wks) and aged (>60 wks) heterozygous and homozygous R349P desmin knock-in mice in comparison to wild-type littermates. We used a novel automated biomechatronics platform, the MyoRobot, to perform coherent quantitative recordings of passive (resting length-tension curves, visco-elasticity) and active (caffeine-induced force transients, pCa-force, 'slack-tests') parameters to determine age-dependent effects of the R349P desmin mutation in slow-twitch soleus and fast-twitch extensor digitorum longus small fiber bundles. We demonstrate that active force properties are not affected by this mutation while passive steady-state elasticity is vastly altered in R349P desmin fiber bundles compatible with a pre-aged phenotype exhibiting stiffer muscle preparations. Visco-elasticity on the other hand, was not altered. Our study represents the first systematic age-related characterization of small muscle fiber bundle preparation biomechanics in conjunction with inherited desminopathy.

Characterization of an antigenic serine protease in the Trichinella spiralis adult.

Serine proteases have been identified as important molecules that are involved in many parasitic infections, and these molecules have also been suggested to play important roles in Trichinella spiralis infections. In the present study, the antigenic serine protease gene Ts-ADSp-7, which was screened from a cDNA library of Trichinella spiralis Adults at 3 days post-infection (p.i.), was cloned and expressed in Escherichia coli. The encoded protein, Ts-ADSp-7, revealed a potential trypsin-like serine protease domain but lacked substrate banding site at position 227 and protease activity. Transcription could be detected in the Adult and muscle larval stage but not in the newborn larval stage, where no fluorescent signal was detected. Western blot analysis revealed that the 3 days p.i. Adults and muscle larvae could secrete Ts-ADSp-7. Interestingly, strong fluorescent signal of Ts-ADSp-7 could be detected in the nucleoli of the enlarged muscle cell nuclei from 12 to 16 days p.i. and in the ß-stichosomes of the muscle larvae from 16 to 35 days p.i.. The coagulation assay indicated that Ts-ADSp-7 could inhibit intrinsic coagulation pathway. Regarding the putatively important function of the serine protease in the helminth infection to hosts, a total of 81 serine proteases were found in the parasite and mainly comprised eight subfamilies. These subfamilies exhibited high similarity to transmembrane serine protease, coagulation factor XI, lipocalin, guanylin, ceropin, kallikrein, and plasminogen. Moreover, stage specificity was detected in several subfamilies. In summary, the putatively inactive serine protease-like protein Ts-ADSp-7 could inhibit blood coagulation, and the protein is located in the enlarged nuclei of nurse cells during capsule formation. Furthermore, members of the serine protease family in the parasite might be important molecules in the parasite-host interaction.

Ultrastructural preservation of tissues and their reaction to the infection with trichinella in the El Plomo mummy: Muscle fiber ultrastructure and trichinosis/mummy of the Cerro El Plomo.

The El Plomo mummy was a pre-Columbian Incan child who was found mummified in the Andes Mountains above an altitude of 17,700 feet. In the environment, natural mummification occurred due to low temperatures and strong winds. Dating measurements (relative dating) by experts from the National Museum of Natural History of Chile established that the mummified body corresponds the Inca period (1,450 to 1,500 AD). In 2003, the body was transferred to the University of Chile Medical School for exhaustive medical examination. Tissue samples from the right quadriceps muscle were extracted and fixed in glutaraldehyde and postfixed in osmium tetroxide to obtain ultrathin sections to be observed by transmission electron microscope. Images were recorded on photographic paper, digitalized and analyzed by experts on morphology. Results showed a preservation of cell boundaries in striated muscle cells, but specific subcellular organelles or contractile sarcomeric units (actin and myosin) were unable to be recognized. However, the classical ultrastructural morphology of the polypeptide collagen type I was preserved intact both in primary and secondary organization. Therefore, we concluded that the process of natural mummification by freezing and strong winds is capable of damaging the ultrastructure of muscle cells and preserving collagen type I intact.

The unfolded protein response in relation to mitochondrial biogenesis in skeletal muscle cells.

Mitochondria comprise both nuclear and mitochondrially encoded proteins requiring precise stoichiometry for their integration into functional complexes. The augmented protein synthesis associated with mitochondrial biogenesis results in the accumulation of unfolded proteins, thus triggering cellular stress. As such, the unfolded protein responses emanating from the endoplasmic reticulum (UPRER) or the mitochondrion (UPRMT) are triggered to ensure correct protein handling. Whether this response is necessary for mitochondrial adaptations is unknown. Two models of mitochondrial biogenesis were used: muscle differentiation and chronic contractile activity (CCA) in murine muscle cells. After 4 days of differentiation, our findings depict selective activation of the UPRMT in which chaperones decreased; however, Sirt3 and UPRER markers were elevated. To delineate the role of ER stress in mitochondrial adaptations, the ER stress inhibitor TUDCA was administered. Surprisingly, mitochondrial markers COX-I, COX-IV, and PGC-1α protein levels were augmented up to 1.5-fold above that of vehicle-treated cells. Similar results were obtained in myotubes undergoing CCA, in which biogenesis was enhanced by ~2-3-fold, along with elevated UPRMT markers Sirt3 and CPN10. To verify whether the findings were attributable to the terminal UPRER branch directed by the transcription factor CHOP, cells were transfected with CHOP siRNA. Basally, COX-I levels increased (~20%) and COX-IV decreased (~30%), suggesting that CHOP influences mitochondrial composition. This effect was fully restored by CCA. Therefore, our results suggest that mitochondrial biogenesis is independent of the terminal UPRER Under basal conditions, CHOP is required for the maintenance of mitochondrial composition, but not for differentiation- or CCA-induced mitochondrial biogenesis.

Haycocknema perplexum: an emerging cause of parasitic myositis in Australia.

Haycocknema perplexum is a rare cause of parasitic myositis, with all cases of human infection reported from Australia. This case involved an 80-year-old Queensland wildlife carer, who presented with muscle weakness, mild eosinophilia and creatine kinase elevation. This case supports an association with native animal contact and highlights the debilitating nature of this infection.

Toxoplasma gondii within skeletal muscle cells: a critical interplay for food-borne parasite transmission.

Toxoplasma gondii infects virtually any nucleated cell type of warm-blooded animals and humans including skeletal muscle cells (SkMCs). Infection of SkMCs by T. gondii, differentiation from the highly replicative tachyzoites to dormant bradyzoites and tissue cyst formation are crucial for parasite persistence in muscle tissue. These processes are also prerequisites for one of the major routes of transmission to humans via undercooked or cured meat products. Evidence obtained in vitro and in vivo indicates that SkMCs are indeed a preferred cell type for tissue cyst formation and long-term persistence of T. gondii. This raises intriguing questions about what makes SkMCs a suitable environment for parasite persistence and how the SkMC-T. gondii interaction is regulated. Recent data from our laboratory show that differentiation of SkMCs from myoblasts to syncytial myotubes, rather than the cell type itself, is critical for parasite growth, bradyzoite formation and tissue cyst maturation. Myotube formation is accompanied by a permanent withdrawal from the cell cycle, and the negative cell cycle regulator cell division autoantigen (CDA)-1 directly or indirectly promotes T. gondii stage conversion in SkMCs. Moreover, host cell cycle regulators are specifically modulated in mature myotubes, but not myoblasts, following infection. Myotubes also up-regulate the expression of various pro-inflammatory cytokines and chemokines after T. gondii infection and they respond to IFN-γ by exerting potent anti-parasitic activity. This highlights that mature myotubes are active participants rather than passive targets of the local immune response to T. gondii which may also govern the interaction between SkMCs and the parasite.

Trichosomoides nasalis (Nematoda: Trichinelloidea) in the murid host Arvicanthis niloticus: migration to the epithelium of the nasal mucosa after intramuscular development.

Knowledge of the biology of the trichinelloid subfamily Trichosomoidinae is poor. Trichosomoides nasalis is a common parasite of Arvicanthis niloticus (Muridae) in Senegal, and a procedure for experimental infections has been established. It has been demonstrated that larvae develop in striated muscle fibres, similar to Trichinella spp., but they are not arrested in the first stage, and they reach the adult stage within three weeks. In the present histological study it is shown that T. nasalis females and dwarf males migrate from the abdomen and thorax to the host's muzzle, moving through connective tissues and between muscles. A few migrating specimens were also found in the blood vessels of the nasal mucosa. While sexes were still separated in the lamina propria of the mucosa, females recovered from the epithelium contained intra-uterine males. Worms were found between the incisors in the mucosa of the anterior and median conchae which are rich in mucous cells. Only the pseudostratified epithelium was parasitized. Under natural conditions, the inflammation of the nasal mucosa that is induced by the parasites might reduce the competitiveness of infected rodents when foraging or looking for potential mates.

Toxoplasma gondii down modulates cadherin expression in skeletal muscle cells inhibiting myogenesis.

BACKGROUND: Toxoplasma gondii belongs to a large and diverse group of obligate intracellular parasitic protozoa. Primary culture of mice skeletal muscle cells (SkMC) was employed as a model for experimental toxoplasmosis studies. The myogenesis of SkMC was reproduced in vitro and the ability of T. gondii tachyzoite forms to infect myoblasts and myotubes and its influence on SkMC myogenesis were analyzed. RESULTS: In this study we show that, after 24 h of interaction, myoblasts (61%) were more infected with T. gondii than myotubes (38%) and inhibition of myogenesis was about 75%. The role of adhesion molecules such as cadherin in this event was investigated. First, we demonstrate that cadherin localization was restricted to the contact areas between myocytes/myocytes and myocytes/myotubes during the myogenesis process. Immunofluorescence and immunoblotting analysis of parasite-host cell interaction showed a 54% reduction in cadherin expression at 24 h of infection. Concomitantly, a reduction in M-cadherin mRNA levels was observed after 3 and 24 h of T. gondii-host cell interaction. CONCLUSIONS: These data suggest that T. gondii is able to down regulate M-cadherin expression, leading to molecular modifications in the host cell surface that interfere with membrane fusion and consequently affect the myogenesis process.

Leishsmania (Leishmania) amazonensis infection: Muscular involvement in BALB/c and C3H.HeN mice.

Recent studies have provided some insights into Leishsmania (Leishmania) amazonensis muscular infection in dogs, although, muscular disease due to leishmaniasis has been poorly documented. The aim of our study was to evaluate involvement of Leishmania in muscular infection of two distinct mouse strains (BALB/c and C3H.He), with different genetic backgrounds. BALB/c mice, susceptible to Leishmania infection, showed, at the beginning of infection, a great number of infected macrophages among muscle fibers; however, in C3H.He resistant mice, muscle fibers were less damaged than in BALB/c mice, but some parasitized macrophages could be seen among them. A follow up of the infection showed an intense inflammatory infiltrate mainly composed of infected macrophages in BALB/c muscles and the presence of amastigotes within muscle fibers; while C3H.He mice exhibited a moderate inflammatory infiltrate among skeletal muscle fibers and an absence of amastigotes. Total destruction of muscles was observed in BALB/c mice in the late phase of infection (day 90) while C3H.He mice showed a process of muscle repair. We concluded that: (1) the muscles of BALB/c mice were more affected by leishmaniasis than those of C3/H.He mice; (2) Leishmania amastigotes are capable of infecting muscular fibers, as observed in BALB/c mice; (3) as inflammatory infiltrate is less intense in C3H.He mice these animals are capable of restoring muscular fibers.

Spontaneous stage differentiation of mouse-virulent Toxoplasma gondii RH parasites in skeletal muscle cells: an ultrastructural evaluation.

Although the predilection for Toxoplasma gondii to form cysts in the nervous system and skeletal and heart muscles has been described for more than fifty years, skeletal muscle cells (SkMCs) have not been explored as a host cell type to study the Toxoplasma-host cell interaction and investigate the intracellular development of the parasite. Morphological aspects of the initial events in the Toxoplasma-SkMC interaction were analysed and suggest that there are different processes of protozoan adhesion and invasion and of the subsequent fate of the parasite inside the parasitophorous vacuole (PV). Using scanning electron microscopy,Toxoplasma tachyzoites from the mouse-virulent RH strain were found to be attached to SkMCs by the anterior or posterior region of the body, with or without expansion of the SkMC membrane. This suggests that different types of parasite internalization occurred. Asynchronous multiplication and differentiation of T. gondii were observed. Importantly, intracellular parasites were seen to display high amounts of amylopectin granules in their cytoplasm, indicating that tachyzoites of the RH strain were able to differentiate spontaneously into bradyzoites in SkMCs. This stage conversion occurred in approximately 3% of the PVs. This is particularly intriguing as tachyzoites of virulent Toxoplasma strains are not thought to be prone to cyst formation. We discuss whether biological differences in host cells are crucial to Toxoplasma stage conversion and suggest that important questions concerning the host cell type and its relevance in Toxoplasma differentiation are still unanswered.

Spontaneous stage differentiation of mouse-virulent Toxoplasma gondii RH parasites in skeletal muscle cells: an ultrastructural evaluation

Although the predilection for Toxoplasma gondii to form cysts in the nervous system and skeletal and heart muscles has been described for more than fifty years, skeletal muscle cells (SkMCs) have not been explored as a host cell type to study the Toxoplasma-host cell interaction and investigate the intracellular development of the parasite. Morphological aspects of the initial events in the Toxoplasma-SkMC interaction were analysed and suggest that there are different processes of protozoan adhesion and invasion and of the subsequent fate of the parasite inside the parasitophorous vacuole (PV). Using scanning electron microscopy,Toxoplasma tachyzoites from the mouse-virulent RH strain were found to be attached to SkMCs by the anterior or posterior region of the body, with or without expansion of the SkMC membrane. This suggests that different types of parasite internalization occurred. Asynchronous multiplication and differentiation of T. gondii were observed. Importantly, intracellular parasites were seen to display high amounts of amylopectin granules in their cytoplasm, indicating that tachyzoites of the RH strain were able to differentiate spontaneously into bradyzoites in SkMCs. This stage conversion occurred in approximately 3 percent of the PVs. This is particularly intriguing as tachyzoites of virulent Toxoplasma strains are not thought to be prone to cyst formation. We discuss whether biological differences in host cells are crucial to Toxoplasma stage conversion and suggest that important questions concerning the host cell type and its relevance in Toxoplasma differentiation are still unanswered.

Primary skeletal muscle cells trigger spontaneous Toxoplasma gondii tachyzoite-to-bradyzoite conversion at higher rates than fibroblasts.

Toxoplasma gondii is one of the most common eukaryotic parasites and an important opportunistic pathogen of humans. The interconversion from proliferative tachyzoites into quiescent encysted bradyzoites plays pivotal roles in the lifelong persistence of T. gondii in its host and the pathogenesis of toxoplasmosis. Stage conversion and persistence in skeletal muscle tissue may be particularly important for the food-borne transmission of T. gondii to humans via raw or undercooked meat products. Here, we have followed the transition of tachyzoites to bradyzoites after infection of skeletal muscle cells (SkMC). Primary murine myoblasts were differentiated to multinucleated syncytial myotubes that displayed regular contractions in vitro and expressed myogenic markers Myf5 and MyoD. Tachyzoites of T. gondii invaded SkMC within 4h of infection and started to replicate within 24h of infection. Remarkably, intracellular tachyzoites readily differentiated to bradyzoites in SkMC without the need of exogenous stress factors. Double immunofluorescence labelling revealed significantly higher percentages of bradyzoite-containing vacuoles in SkMC than in murine fibroblasts at 24h until 6 days after infection. Furthermore, transcript levels of bradyzoite-specific ENO1 but not tachyzoite-specific ENO2 strongly increased in T. gondii-infected SkMC until 6 days of infection. These findings indicate that the commitment of T. gondii to differentiate to bradyzoites in SkMC does not require exogenous stress factors but could be rather regulated by cell-type specific factors.

Canine inflammatory myopathy associated with Leishmania Infantum infection.

Inflammatory myopathy associated with several infectious diseases occurs in dogs including those caused by Toxoplasma gondii, Neospora caninum, Ehrlichia canis and Hepatozoon canis. However, muscle disease due to Leishmania infection has been poorly documented. The aim of this study was to examine the distribution and types of cellular infiltrates and expression of MHC class I and II in muscle biopsies obtained from 15 male beagle dogs from a breeder group with an established diagnosis of leishmaniasis. Myopathic features were characterized by necrosis, regeneration, fibrosis and infiltration of mononuclear inflammatory cells consisting of lymphocytes, plasma cells and histiocytes. The predominant leukocyte populations were CD3+, CD8+ and CD45RA+ with lesser numbers of CD4+ cells. Many muscle fibers had MHC class I and II positivity on the sarcolemma. There was a direct correlation between the severity of pathological changes, clinical signs, and the numbers of Leishmania amastigotes. Our studies provided evidence that: 1) Leishmania should be considered as a cause of IM in dogs; 2) Leishmania is not present within muscle fibers but in macrophages, and that 3) the muscle damage might be related to immunological alterations associated with Leishmania infection. Leishmania spp. should also be considered as a possible cause in the pathogenesis of human myositis.

Haycocknema-like nematodes in muscle fibres of a horse.

A 14-year-old horse (imported to Switzerland from Ireland 8 years earlier) showed signs of chewing muscle atrophy. A severe chronic myositis, caused by numerous immature and mature female nematodes, was diagnosed in muscle samples obtained by biopsy and subsequently at necropsy. Most of the nematodes had invaded muscle fibres of the masseter, root of the tongue and anterior breast, only a few were found in the intermuscular interstitium. Isolated nematodes and parasite sections were clearly different from muscle larvae of Trichinella spp. but showed morphological similarities to Haycocknema perplexum, a nematode species (order Enoplida, family Robertdollfusidae) recently found in the musculature of a human patient in Australia. However, our material did not allow the precise identification of the nematode genus nor the unequivocal differentiation from Halicephalobus gingivalis. This species infects horses and humans and can cause severe granuloma formation in muscles and many other organ systems, but has never been observed to invade individual muscle fibres. Our findings show that nematodes of another genus than Trichinella may invade muscle fibres of the horse and cause myositis. These nematodes are provisionally regarded as Haycocknema-like.

Response of ADA and its isoenzymes in mice infected by Trichinella spiralis and treated with mimosine.

Infections caused by the nematode Trichinella spiralis (T. spiralis) are characterized by an inflammatory response in the host. The aim of this study was to identify and evaluate markers for monitoring mice infected with T. spiralis and treated with or without mimosine. The markers that have been used were total and differential white blood cell counts, subpopulations of lymphocytes, serum tADA and its isoenzymes ADA1 and ADA2 activity. The study included 3 groups of BALB/c mice. Group A consisted of 16 healthy mice, Group B of 16 mice infected with T. spiralis and treated with saline, and Group C of 16 mice infected with T. spiralis and treated with mimosine. The measurements were made once per week for the first six weeks continuously following the infection. According to our results, leukocytosis, lymphocytosis and increased percentages of adhesion molecules and CD4 lymphocytes were present in groups B and C one week post-infection. Total ADA activity as well as ADA1 and ADA2 was higher in groups B and C versus group A from the first week post-infection. The levels of tADA activity, ADA1 and ADA2 were higher in group B compared to those of group C and the difference was statistically significant (p<0.05) during the 4th week post-infection. The majority of tADA activity, essential for an efficient immune response, was derived from ADA1 which may have been produced by infected tissues. The elevated activities of tADA and ADA1 may be sensitive markers for infection of T. spiralis and for monitoring the course of the infection.

Skeletal muscle pathology in 2 siblings infected with Toxoplasma gondii.

Skeletal muscle can be the site of inflammatory diseases that lead to muscle weakness, pain, and increased myogenic serum enzymes. Most of these inflammatory myopathies are idiopathic. In some cases inflammatory myopathies are due to infectious agents. We describe the pathological aspects of muscle biopsies of 2 Brazilian siblings who acquired toxoplasmosis at the same time and in similar conditions. One developed a tetraplegia that was confirmed to be due to inflammatory myositis due to toxoplasma. The other developed myocarditis, with heart failure, without skeletal muscle weakness. In both cases many toxoplasma organisms were observed in the muscle biopsies, but in case 1 only was there an inflammatory myopathy with myofiber necrosis; the inflammatory cells were predominantly macrophages with some CD4+ cells and rare CD20+ cells. In case 1, expression of CD54 was observed in many inflammatory cells as well in endothelial cells, but only in endothelial cells in case 2. After treatment with clindamycin and corticosteroids both cases had only partial improvement, case 1 with a residual muscle weakness and case 2 with residual cardiac insufficiency (requiring digoxin). These cases show that the presence of the parasite in myofibers is not enough to induce an inflammatory myositis with muscle cell necrosis. This suggests that immunological disturbances may contribute to the development of inflammatory myositis due to toxoplasma.

[The effect of coccidia of the genus Sarcocystis on the morphofunctional organization of the skeletal musculature in experimentally infected mice. I. The muscle fiber]. / Vliianie koktsidii roda Sarcocystis na morfofunktsional'nuiu organizatsiiu skeletnoi muskulatury éksperimental'no zarazhennykh myshei. I. Myshechnoe volokno.

At the ultrastructural level, the cellular response of skeletal muscles on developing Sarcocystis muris sarcocysts has been followed in mice at different times after sporocyst feeding, i.e. in 1, 2.5, 6 and 10 months, resp. The developing cyst creates a progressive degeneration of the infected muscle cell that involves organelle disorganization and formation of numerous vacuoles in the cytoplasm as a consequence of cell edema. Products of the host cell degradation, shaped as fibrillar-granular structures, are seen to find their way to the cyst wall outgrowings, where they become denser and on being covered with membranes appear eventually in the sarcocyst ground substance. Later on, the membranes around the granules disappear. In the course of its development, the sarcocyst totally destroys not only the harbouring muscle cell and the nearest connective tissue elements of the endomysium, but also the previously intact neighbouring cells. The involvement of some proteolytic enzymes in this process is suggested.

[The effect of coccidia of the genus Sarcocystis on the morphofunctional organization of the skeletal musculature in experimentally infected mice. II. The connective tissue elements of the endomysium]. / Vliianie koktsidii roda Sarcocystis na morfofunktsional'nuiu organizatsiiu skeletnoi muskulatury éksperimental'no zarazhennykh myshei. II. Soedinitel'notkannye élementy éndomiziia.

As an extension of the previous communication (Radchenko, et al., 1996), a study was made of the response of connective tissue elements, surrounding the Sarcocystis muris infected muscle fibers. As earlier, the S. muris sarcocysts were examined in mice 1, 2.5, 6, and 10 months after sporocyst feeding. Within the first 2.5 months after infection, marked accumulations of lymphocyte-like cells and collagen fibres are observed in the endomysium, and simultaneously the activity of capillary endothelial cells is seen to enhance due to the appearance of much more micropinocytotic vesicles, compared to the uninfected control. All this may be qualified as the host organism protective reaction to the parasitic infection. 6 and 10 months after infection, not only collagen fibres, but also some other fibrillar structures of the endomysium undergo degradation, the damage of capillary endothelial cells starting from breaking the outer membrane (in 6 months) and terminating in lysing the whole cell (in 10 months). Besides, structural abnormalities were noticed in the axon endings.