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1.
Carvalho CM Silverio JC da Silva AA Pereira IR Coelho JM Britto CC Moreira OC Marchevsky RS Xavier SS Gazzinelli RT da Glória Bonecini-Almeida M Lannes-Vieira J 《PLoS neglected tropical diseases》2012,6(5):e1644
Background
The factors contributing to chronic Chagas'' heart disease remain unknown. High nitric oxide (NO) levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2) is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2 −/−) mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection.Methodology
Rhesus monkeys and C57BL/6 and Nos2 −/− mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2+ cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG), echocardiogram (ECHO), creatine kinase heart isoenzyme (CK-MB) activity levels in serum and connexin 43 (Cx43) expression in the cardiac tissue.Results
Chronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC). Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2+ cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2 −/− mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue.Conclusion
T. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute to CCC severity, mainly disturbing of the molecular pathway involved in electrical synchrony. These findings open a new avenue for therapeutic tools in Chagas'' heart disease. 相似文献2.
Antonio Gigliotti Rothfuchs Ester Roffê Amanda Gibson Allen W. Cheever R. Alan B. Ezekowitz Kazue Takahashi Mario Steindel Alan Sher André Báfica 《PloS one》2012,7(11)
Mannose-binding lectin (MBL) is a humoral pattern-recognition molecule important for host defense. Although recent genetic studies suggest an involvement of MBL/MASP2-associated pathways in Chagas’ disease, it is currently unknown whether MBL plays a role in host resistance to the intracellular protozoan Trypanosoma cruzi, the causative agent of Chagas’ disease. In this study we employed MBL−/− mice to assess the role of MBL in resistance to experimental infection with T. cruzi. T. cruzi infection enhanced tissue expression of MBL both at the mRNA and protein level. Similarly, symptomatic acute Chagas’ disease patients displayed increased serum concentrations of MBL compared to patients with indeterminate, asymptomatic forms of the disease. Furthermore, increased parasite loads in the blood and/or tissue were observed in MBL−/− mice compared to WT controls. This was associated with reduced systemic levels of IL-12/23p40 in MBL−/− mice. Importantly, MBL−/− mice infected with a cardiotropic strain of T. cruzi displayed increased myocarditis and cardiac fibrosis compared to WT controls. The latter was accompanied by elevated hydroxyproline content and mRNA levels of collagen-1 and -6 in the heart. These observations point to a previously unappreciated role for MBL in regulating host resistance and cardiac inflammation during infection with a major human pathogen. 相似文献
3.
Dean S. Cunningham Raymond E. Kuhn Rick L. Tarleton Rebakah S. Dunn 《Experimental parasitology》1981,51(2):257-268
During the course of Trypanosoma cruzi infection in C57BL/6 mice, which are relatively resistant to the parasite, the hosts developed antibody activity against previously unencountered antigens. The anti-sheep erythrocyte and antitrinitrophenyl antibody levels increased rapidly from Day 7 of infection, reached a peak by the 21st day, and were maintained at this level through 120 days postinfection in these mice. In contrast, highly susceptible C3H(He) mice did not have demonstrable antibody responses to SRBC or TNP during the 24-day infection period. Autoantibody activity against the selfantigens presented on isologous erythrocytes or thymocytes, however, were reduced in infected C57BL/6 mice. No significant reduction in autoreactivity to the self-antigens on erythrocytes or thymocytes was observed in C3H(He) mice infected with T. cruzi although a trend of reduced autoresponsiveness toward erythrocytes appeared to be developing by the time of death. C57BL/6 mice immunized with sheep erythrocytes as neonates and infected with T. cruzi as adults, or adult mice primed with low doses of sheep erythrocytes prior to infection, had elevated antibody responses to sheep erythrocytes unless the mice were immunized with sheep erythrocytes during the course of infection, in which case suppression of the response against sheep erythrocytes resulted. The nonspecific synthesis of immunoglobulins in infected C57BL/6 mice was, in part, a result of the lymphocyteactivating properties of T. cruzi-associated antigens. The T. cruzi-associated antigens induced proliferative and differentiative responses in spleen cells in vitro. It is proposed that the T. cruzi-associated antigens differentially affect lymphocytes capable of responding to antigen and those lymphocytes previously stimulated by antigen. 相似文献
4.
Isabela Resende Pereira Glaucia Vilar-Pereira Virgínia Marques Andrea Alice da Silva Bráulia Caetano Otacilio Cruz Moreira Alexandre Vieira Machado Oscar Bruna-Romero Maurício Martins Rodrigues Ricardo Tostes Gazzinelli Joseli Lannes-Vieira 《PLoS pathogens》2015,11(1)
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a prototypical neglected tropical disease. Specific immunity promotes acute phase survival. Nevertheless, one-third of CD patients develop chronic chagasic cardiomyopathy (CCC) associated with parasite persistence and immunological unbalance. Currently, the therapeutic management of patients only mitigates CCC symptoms. Therefore, a vaccine arises as an alternative to stimulate protective immunity and thereby prevent, delay progression and even reverse CCC. We examined this hypothesis by vaccinating mice with replication-defective human Type 5 recombinant adenoviruses (rAd) carrying sequences of amastigote surface protein-2 (rAdASP2) and trans-sialidase (rAdTS) T. cruzi antigens. For prophylactic vaccination, naïve C57BL/6 mice were immunized with rAdASP2+rAdTS (rAdVax) using a homologous prime/boost protocol before challenge with the Colombian strain. For therapeutic vaccination, rAdVax administration was initiated at 120 days post-infection (dpi), when mice were afflicted by CCC. Mice were analyzed for electrical abnormalities, immune response and cardiac parasitism and tissue damage. Prophylactic immunization with rAdVax induced antibodies and H-2Kb-restricted cytotoxic and interferon (IFN)γ-producing CD8+ T-cells, reduced acute heart parasitism and electrical abnormalities in the chronic phase. Therapeutic vaccination increased survival and reduced electrical abnormalities after the prime (analysis at 160 dpi) and the boost (analysis at 180 and 230 dpi). Post-therapy mice exhibited less heart injury and electrical abnormalities compared with pre-therapy mice. rAdVax therapeutic vaccination preserved specific IFNγ-mediated immunity but reduced the response to polyclonal stimuli (anti-CD3 plus anti-CD28), CD107a+ CD8+ T-cell frequency and plasma nitric oxide (NO) levels. Moreover, therapeutic rAdVax reshaped immunity in the heart tissue as reduced the number of perforin+ cells, preserved the number of IFNγ+ cells, increased the expression of IFNγ mRNA but reduced inducible NO synthase mRNA. Vaccine-based immunostimulation with rAd might offer a rational alternative for re-programming the immune response to preserve and, moreover, recover tissue injury in Chagas’ heart disease. 相似文献
5.
Maria T. Ronco Daniel E. Francés Paola I. Ingaramo Ariel D. Quiroga Maria L. Alvarez Gerardo B. Pisani Silvia S. Revelli Cristina E. Carnovale 《Cytokine》2010,49(1):64-72
Trypanosoma cruzi (T. cruzi) infected C57BL/6 mice developed a progressive fatal disease due to an imbalance in the profile of circulating related compounds accompanying infection like tumor necrosis factor alpha (TNFα). TNFα has been proposed as an important effector molecule in apoptosis. In this work, we evaluate inflammation and the proteins involved in apoptotic process in liver of infected mice and the role of TNFα. C57BL6/mice were infected subcutaneously with 100 viable trypomastigotes of Tulahuén strain of T cruzi. One set of these animals were treated with 375 μg of antihuman TNFα blocking antibody. Animals were sacrificed at 14 days post-infection (p.i).The analyses of Bcl-2 family proteins revealed an increase of the pro-apoptotic proteins Bax and tBid in T. cruzi-infected mice. Compared with control animals, cytochrome c release was increased. Apoptosis was also induced in infected mice. Anti-TNFα treatment decreases hepatic apoptosis. Our results suggest that T. cruzi infection induces programmed cell death in the host liver by increase of TNFα production, associated with TNF-R1 over-expression, that set in motion the Bid cleavage and mitochondrial translocation, Bax mitochondrial translocation, cytochrome c release, and ultimately apoptosis induction. 相似文献
6.
Martha Elba Gonzalez-Mejia Enrique Torres-Rasgado Leonardo M Porchia Hilda Rosas Salgado José-Luis Totolhua Arturo Ortega Luisa Clara Regina Hernández-Kelly Guadalupe Ruiz-Vivanco Blanca G Báez-Duarte Ricardo Pérez-Fuentes 《Memórias do Instituto Oswaldo Cruz》2014,109(2):174-181
Chagas disease, caused by Trypanosoma cruzi, represents an endemic
among Latin America countries. The participation of free radicals, especially nitric
oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals
with T. cruzi. In Chagas disease, increased NO contributes to the
development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient
free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine
model of the chronic phase of Chagas disease using endemic T. cruzi
RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated
(Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME
treated and non-infected vehicle-treated. We determined blood parasitaemia and NO
levels, the extent of parasite nests in tissues and liver MT-I expression levels. It
was observed that NO levels were increasing in Inf mice in a time-dependent manner.
Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal
muscle with decreased blood NO levels at day 135 post infection. This affect was
negatively correlated with an increase of MT-I expression (r = -0.8462, p <
0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory
mechanism reduces MT-I expression, allowing augmented NO levels. 相似文献
7.
Carolina Panis Tânia Longo Mazzuco Cauê Zortéa Fernandes Costa Vanessa Jacob Victorino Vera Lúcia Hideko Tatakihara Lucy Megumi Yamauchi Sueli Fumie Yamada-Ogatta Rubens Cecchini Luiz Vicente Rizzo Phileno Pinge-Filho 《Experimental parasitology》2011,(1):58-65
Leukotrienes are important mediators of inflammatory responses. In this study, we investigated the effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on levels of cytokines, nitric oxide (NO) and iNOS expression in cardiac tissue of mice infected with Trypanosoma cruzi, the agent of Chagas’ disease. NO is a key mediator of parasite killing in mice experimentally infected with T. cruzi, and previous studies have suggested that leukotrienes, such as LTB4, induces NO synthesis in T. cruzi-infected macrophages and plays a relevant role in the killing of parasite in a NO-dependent manner. We therefore investigated whether leukotrienes would have a similar role in vivo in controlling the parasite burden by regulating NO activity. We have made the striking observation that absence of 5-LO-derived leukotrienes results in increased NO and IL-6 production in the plasma with a concomitant decrease in the expression of iNOS in the cardiac tissue on day 12 after T. cruzi infection. These findings indicate that endogenous leukotrienes are important regulators of NO activity in the heart and therefore influence the cardiac parasite burden without exerting a direct action on IL-6 production in the acute phase of infection with T. cruzi. 相似文献
8.
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects several million people in Latin America. Myocarditis, observed during both the acute and chronic phases of the disease, is characterized by an inflammatory mononuclear cell infiltrate that includes CD4+ T cells. It is known that Th1 cytokines help to control infection. The role that Treg and Th17 cells may play in disease outcome, however, has not been completely elucidated. We performed a comparative study of the dynamics of CD4+ T cell subsets after infection with the T. cruzi Y strain during both the acute and chronic phases of the disease using susceptible BALB/c and non-susceptible C57BL/6 mice infected with high or low parasite inocula. During the acute phase, infected C57BL/6 mice showed high levels of CD4+ T cell infiltration and expression of Th1 cytokines in the heart associated with the presence of Treg cells. In contrast, infected BALB/c mice had a high heart parasite burden, low heart CD4+ T cell infiltration and low levels of Th1 and inflammatory cytokines, but with an increased presence of Th17 cells. Moreover, an increase in the expression of IL-6 in susceptible mice was associated with lethality upon infection with a high parasite load. Chronically infected BALB/c mice continued to present higher parasite burdens than C57BL/6 mice and also higher levels of IFN-γ, TNF, IL-10 and TGF-β. Thus, the regulation of the Th1 response by Treg cells in the acute phase may play a protective role in non-susceptible mice irrespective of parasite numbers. On the other hand, Th17 cells may protect susceptible mice at low levels of infection, but could, in association with IL-6, be pathogenic at high parasite loads. 相似文献
9.
Roles of tumor necrosis factor alpha (TNF-alpha) and the p55 TNF receptor in CD1d induction and coxsackievirus B3-induced myocarditis
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Giving C57BL/6 mice 10(4) PFU of coxsackievirus B3 (H3 variant) fails to induce myocarditis, but increasing the initial virus inoculum to 10(5) or 10(6) PFU causes significant cardiac disease. Virus titers in the heart were equivalent at days 3 and 7 in mice given all three virus doses, but day 3 titers in the pancreases of mice inoculated with 10(4) PFU were reduced. Tumor necrosis factor alpha (TNF-alpha) concentrations in the heart were increased in all infected mice, but cytokine levels were highest in mice given the larger virus inocula. TNF-alpha(-/-) and p55 TNF receptor-negative (TNFR(-/-)) mice developed minimal myocarditis compared to B6;129 or C57BL/6 control mice. p75 TNFR(-/-) mice were as disease susceptible as C57BL/6 animals. No significant differences in virus titers in heart or pancreas were observed between the groups, but C57BL/6 and p75 TNFR(-/-) animals showed 10-fold more inflammatory cells in the heart than p55 TNFR(-/-) mice, and the cell population was comprised of high concentrations of CD4(+) gamma interferon-positive and Vgamma4(+) cells. Cardiac endothelial cells isolated from C57BL/6 and p75 TNFR(-/-) mice upregulate CD1d, the molecule recognized by Vgamma4(+) cells, but infection of TNF(-/-) or p55 TNFR(-/-) endothelial cells failed to upregulate CD1d. Infection of C57BL/6 endothelial cells with a nonmyocarditic coxsackievirus B3 variant, H310A1, which is a poor inducer of TNF-alpha, failed to elicit CD1d expression, but TNF-alpha treatment of H310A1-infected endothelial cells increased CD1d levels to those seen in H3-infected cells. TNF-alpha treatment of uninfected endothelial cells had only a modest effect on CD1d expression, suggesting that optimal CD1d upregulation requires both infection and TNF-alpha signaling. 相似文献
10.
Host and parasite genetics shape a link between Trypanosoma cruzi infection dynamics and chronic cardiomyopathy
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Michael D. Lewis Amanda Fortes Francisco Martin C. Taylor Shiromani Jayawardhana John M. Kelly 《Cellular microbiology》2016,18(10):1429-1443
Host and parasite diversity are suspected to be key factors in Chagas disease pathogenesis. Experimental investigation of underlying mechanisms is hampered by a lack of tools to detect scarce, pleiotropic infection foci. We developed sensitive imaging models to track Trypanosoma cruzi infection dynamics and quantify tissue‐specific parasite loads, with minimal sampling bias. We used this technology to investigate cardiomyopathy caused by highly divergent parasite strains in BALB/c, C3H/HeN and C57BL/6 mice. The gastrointestinal tract was unexpectedly found to be the primary site of chronic infection in all models. Immunosuppression induced expansion of parasite loads in the gut and was followed by widespread dissemination. These data indicate that differential immune control of T. cruzi occurs between tissues and shows that the large intestine and stomach provide permissive niches for active infection. The end‐point frequency of heart‐specific infections ranged from 0% in TcVI‐CLBR‐infected C57BL/6 to 88% in TcI‐JR‐infected C3H/HeN mice. Nevertheless, infection led to fibrotic cardiac pathology in all models. Heart disease severity was associated with the model‐dependent frequency of dissemination outside the gut and inferred cumulative heart‐specific parasite loads. We propose a model of cardiac pathogenesis driven by periodic trafficking of parasites into the heart, occurring at a frequency determined by host and parasite genetics. 相似文献
11.
《Microbes and infection / Institut Pasteur》2014,16(9):768-777
Previous studies have demonstrated loss/reduction of dystrophin in cardiomyocytes in both acute and chronic stages of experimental Trypanosoma cruzi (T. cruzi) infection in mice. The mechanisms responsible for dystrophin disruption in the hearts of mice acutely infected with T. cruzi are not completely understood. The present in vivo and in vitro studies were undertaken to evaluate the role of inflammation in dystrophin disruption and its correlation with the high mortality rate during acute infection. C57BL/6 mice were infected with T. cruzi and killed 14, 20 and 26 days post infection (dpi). The intensity of inflammation, cardiac expression of dystrophin, calpain-1, NF-κB, TNF-α, and sarcolemmal permeability were evaluated. Cultured neonatal murine cardiomyocytes were incubated with serum, collected at the peak of cytokine production and free of parasites, from T. cruzi-infected mice and dystrophin, calpain-1, and NF-κB expression analyzed. Dystrophin disruption occurs at the peak of mortality and inflammation and is associated with increased expression of calpain-1, TNF-α, NF-κB, and increased sarcolemmal permeability in the heart of T. cruzi-infected mice at 20 dpi confirmed by in vitro studies. The peak of mortality occurred only when significant loss of dystrophin in the hearts of infected animals occurred, highlighting the correlation between inflammation, dystrophin loss and mortality. 相似文献
12.
Romina A. Cutrullis Patricia B. Petray Edgardo Schapachnik Rubén Sánchez Miriam Postan Mariela N. González Valentina Martín Ricardo S. Corral 《PloS one》2013,8(2)
Clinical symptoms of chronic Chagas disease occur in around 30% of the individuals infected with Trypanosoma cruzi and are characterized by heart inflammation and dysfunction. The pathogenesis of chronic chagasic cardiomyopathy (CCC) is not completely understood yet, partially because disease evolution depends on complex host-parasite interactions. Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine that promotes numerous pathophysiological processes. In the current study, we investigated the link between MIF and CCC progression.Immunohistochemical analysis demonstrated MIF overexpression in the hearts from chronically T. cruzi-infected mice, particularly those showing intense inflammatory infiltration. We also found that MIF exogenously added to parasite-infected murine macrophage cultures is capable of enhancing the production of TNF-α and reactive oxygen species, both with pathogenic roles in CCC. Thus, the integrated action of MIF and other cytokines and chemokines may account for leukocyte influx to the infected myocardium, accompanied by enhanced local production of multiple inflammatory mediators. We further examined by ELISA the level of MIF in the sera from chronic indeterminate and cardiomyopathic chagasic patients, and healthy subjects. CCC patients displayed significantly higher MIF concentrations than those recorded in asymptomatic T. cruzi-infected and uninfected individuals. Interestingly, increased MIF levels were associated with severe progressive Chagas heart disease, in correlation with elevated serum concentration of high sensitivity C-reactive protein and also with several echocardiographic indicators of left ventricular dysfunction, one of the hallmarks of CCC. Our present findings represent the first evidence that enhanced MIF production is associated with progressive cardiac impairment in chronic human infection with T. cruzi, strengthening the relationship between inflammatory response and parasite-driven pathology. These observations contribute to unravel the elements involved in the pathogenesis of CCC and may also be helpful for the design of novel therapies aimed to control long-term morbidity in chagasic patients. 相似文献
13.
Kezia Lizardo Janeesh P. Ayyappan Neelam Oswal Louis M. Weiss Philipp E. Scherer Jyothi F. Nagajyothi 《PLoS neglected tropical diseases》2021,15(4)
Chronic Chagas cardiomyopathy (CCC) caused by a parasite Trypanosoma cruzi is a life-threatening disease in Latin America, for which there is no effective drug or vaccine. The pathogenesis of CCC is complex and multifactorial. Previously, we demonstrated T. cruzi infected mice lose a significant amount of fat tissue which correlates with progression of CCC. Based on this an investigation was undertaken during both acute and chronic T. cruzi infection utilizing the FAT-ATTAC murine model (that allows modulation of fat mass) to understand the consequences of the loss of adipocytes in the regulation of cardiac parasite load, parasite persistence, inflammation, mitochondrial stress, ER stress, survival, CCC progression and CCC severity. Mice were infected intraperitoneally with 5x104 and 103 trypomastigotes to generate acute and chronic Chagas models, respectively. Ablation of adipocytes was carried out in uninfected and infected mice by treatment with AP21087 for 10 days starting at 15DPI (acute infection) and at 65DPI (indeterminate infection). During acute infection, cardiac ultrasound imaging, histological, and biochemical analyses demonstrated that fat ablation increased cardiac parasite load, cardiac pathology and right ventricular dilation and decreased survival. During chronic indeterminate infection ablation of fat cells increased cardiac pathology and caused bi-ventricular dilation. These data demonstrate that dysfunctional adipose tissue not only affects cardiac metabolism but also the inflammatory status, morphology and physiology of the myocardium and increases the risk of progression and severity of CCC in murine Chagas disease. 相似文献
14.
Eduardo Mascareno Raavi Gupta Laura A. Martello Manya Dhar-Mascareno Louis Salciccioli Daniel Beckles Michael G. Walsh Fabiana S. Machado Herbert B. Tanowitz M.A. Haseeb 《Microbes and infection / Institut Pasteur》2018,20(1):25-36
Infection with Trypanosoma cruzi causes Chagas disease and results in myocardial inflammation and cardiomyopathy. Downregulated Hexim1 expression, as in Hexim1+/? mice, reduces cardiac inflammation and fibrosis following ischemic stress. We asked whether reduced expression of Hexim1 would also afford protection against T. cruzi-induced cardiomyopathy. C57BL/6J (wild type – WT) and Hexim1+/? mice were infected with sub-lethal doses of T. cruzi (Brazil strain), and cardiac function, serologic markers of inflammation and tissue pathology were examined. Infected Hexim1+/? mice had compromised cardiac function, altered expression of both pro- and anti-inflammatory cytokines, and increased inflammation and fibrosis. Cardiac failure was evidenced by severely diminished heart rate, compensatory increase in respiratory rate, and abnormally high left ventricular mass with severe transmural inflammation. Lungs displayed intense peribronchial inflammation and fibrosis extending into the parenchyma. We also observed Smad3-serine208 phosphorylation in hearts and lungs of infected mice, suggesting increased TGF-β signaling pathway activity. This was more pronounced in Hexim1+/? mice and correlated with increased fibrosis in these tissues. Conspicuous splenomegaly in the Hexim1+/? mice most likely resulted from the observed extensive white pulp expansion. T. cruzi infection induced colonic dilatation and marked villous atrophy in both the WT and Hexim1+/? mice but more so in the latter. The profound exacerbation of pathologic findings suggests a protective role for Hexim1 in T. cruzi infection. 相似文献
15.
Protein fraction from Trypanosoma cruzi infected spleen cell supernatants with immunosuppressive activity in vitro 总被引:2,自引:0,他引:2
Hydro-insoluble protein components of splenocyte supernatants (HPSS) from C3H/He and C57BL/6 mice infected with Trypanosoma cruzi were isolated after diffusion against water and centrifugation. It is strongly suggested that the major component in the precipitate from infected splenocyte cultures, showing a relative mol. wt of 14,000–15,000 and a pI ≌ 6.6 is responsible for the immunosuppressive effect of the blastogenic response to mitogens shown in vitro. It showed its effect across the haplotype barrier (H-2k↔H-2b). Its activity is dose-dependent and its production is related to the period of infection, being 17 days post-infection the date of maximum production by infected splenocytes. Its origin is so far uncertain but seems to be a host product and is probably acting through interaction with normal macrophages, rendering them immunosuppressive. An immunosuppressive protein with similar pI, absent in normal serum, was detected in infected sera. 相似文献
16.
《Microbes and infection / Institut Pasteur》2009,11(2):181-190
We investigated the role of autophagy in infection of macrophages by Leishmania amazonensis. Induction of autophagy by IFN-γ or starvation increased intracellular parasite load and the percentages of infected macrophages from BALB/c but not from C57BL/6 mice. In contrast, starvation did not affect the replication of either Leishmania major or Trypanosoma cruzi in BALB/c macrophages. In BALB/c macrophages, starvation resulted in increased monodansylcadaverine staining and in the appearance of double-membrane and myelin-like vesicles characteristic of autophagosomes. Increased parasite load was associated with a reduction in NO levels and was attenuated by wortmannin, an inhibitor of autophagy. In infected macrophages from BALB/c, but not from C57BL/6 mice, starvation increased the number of lipid bodies and the amounts of PGE2 produced. Exogenous PGE2 increased parasite load in macrophages from BALB/c, but not C57BL/6 mice. The cyclooxygenase inhibitor indomethacin prevented the increase of parasite load in starved BALB/c macrophages, and actually induced parasite killing. These results suggest that autophagy regulates the outcome of L. amazonensis infection in macrophages in a host strain specific manner. 相似文献
17.
Joon-Yong Chung Young-An Bae Doo-Hee Yun Hyun-Jong Yang Yoon Kong 《The Korean journal of parasitology》2012,50(4):301-308
In fascioliasis, T-helper 2 (Th2) responses predominate, while little is known regarding early immune phenomenon. We herein analyzed early immunophenotype changes of BALB/c, C57BL/6, and C3H/He mice experimentally infected with 5 Fasciola hepatica metacercariae. A remarkable expansion of CD19+ B cells was observed as early as week 1 post-infection while CD4+/CD8+ T cells were down-regulated. Accumulation of Mac1+ cells with time after infection correlated well with splenomegaly of all mice strains tested. The expression of tumor necrosis factor (TNF)-α mRNA in splenocytes significantly decreased while that of IL-4 up-regulated. IL-1β expression was down-modulated in BALB/c and C57BL/6 mice, but not in C3H/He. Serum levels of transforming growth factor (TGF)-β were considerably elevated in all mice during 3 weeks of infection period. These collective results suggest that experimental murine fascioliasis might derive immune suppression with elevated levels of TGF-β and IL-4 during the early stages of infection. 相似文献
18.
Trypanosoma cruzi: choline acetyltransferase activity in tissues of susceptible and resistant mice infected with the Brazil strain 总被引:1,自引:0,他引:1
H B Tanowitz P Davies S M Factor T Minase A Herskowitz M Wittner 《Experimental parasitology》1981,51(2):269-278
In order to ascertain if there were biochemical differences in the autonomic nervous system of both C57BL/6-(resistant) and C3H/HeJ-(susceptible) mice infected with the “Brazil” strain of Trypanosoma cruzi we studied the depletion of the enzyme, choline acetyltransferase (EC 2.3.1.6) in the hearts and brains of these infected mice. In the hearts of C3H/HeJ mice, a 30–35% depletion of choline acetyltransferase was evident by day 7 of infection, a time characterized by lack of obvious parasitemia and frank morphological changes in the myocardium or atrial ganglia. When these mice were moribund (day 25) the depletion of choline acetyltransferase was approximately 40%. Myocardial inflammation, necrosis, and increased pseudocyst numbers were evident as the infection proceeded and as the parasitemia rose. In addition, right atrial ganglia were involved with inflammatory cells but were devoid of amastigotes. In resistant (B6) mice choline acetyltransferase levels were not depleted during the course of infection. Brain choline acetyltransferase levels were significantly depleted in moribund C3H mice but there were no frank morphological changes. Extracts of T. cruzi were devoid of any substances capable of inhibiting choline acetyltransferase. Choline acetyltransferase depletion in the hearts of infected susceptible animals precedes morphological alteration. Depletion of this enzyme may be utilized as an early parameter of infection. 相似文献
19.
20.
Behavioural alterations are independent of sickness behaviour in chronic
experimental Chagas disease
Glaucia Vilar-Pereira Leonardo Alexandre de Souza Ruivo Joseli Lannes-Vieira 《Memórias do Instituto Oswaldo Cruz》2015,110(8):1042-1050
The existence of the nervous form of Chagas disease is a matter of discussion since
Carlos Chagas described neurological disorders, learning and behavioural alterations
in Trypanosoma cruzi-infected individuals. In most patients, the
clinical manifestations of the acute phase, including neurological abnormalities,
resolve spontaneously without apparent consequence in the chronic phase of infection.
However, chronic Chagas disease patients have behavioural changes such as psychomotor
alterations, attention and memory deficits, and depression. In the present study, we
tested whether or not behavioural alterations are reproducible in experimental
models. We show that C57BL/6 mice chronically infected with the Colombian strain of
T. cruzi (150 days post-infection) exhibit behavioural changes as
(i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by
elevated plus maze and open field test sand and (iii) motor coordination in the
rotarod test. These alterations are neither associated with neuromuscular disorders
assessed by the grip strength test nor with sickness behaviour analysed by
temperature variation sand weight loss. Therefore, chronically T.
cruzi-infected mice replicate behavioural alterations (depression and
anxiety) detected in Chagas disease patients opening an opportunity to study the
interconnection and the physiopathology of these two biological processes in an
infectious scenario. 相似文献