Parasite load during the acute phase of murine T. cruzi infection determines the activation pattern of the immune system in late chronic phase

ABSTRACT To obtain low and high parasite loads in the acute phase of Chagas’ disease, A/J mice were infected with 103 or 105 Trypanosoma cruzi trypomastigotes of the Y strain and treated on day 6 with benznidazol. One year later, chronically infected mice were screened for subpatent parasitemias, tissue pathology, and immune response. Mice infected with the high parasite inoculum showed higher levels of chronic parasitemias, heart and striated muscle inflammation, and activation of the immune system than did mice infected with the low inoculum. Concerning the activation of the immune system, the main findings for high-dose-infected mice were (i) increased numbers of splenocytes, with preferential expansion of CD8+ and B220− CD5− cells, many of them bearing a macrophage phenotype; (ii) higher frequencies of B (B220+), CD4+, and CD8+ large lymphocytes; (iii) a shift of CD4+ cells towards a CD45RBLow phenotype; (iv) increased frequencies of both CD45RBLow and CD45RBHigh large CD4+cells; (v) augmented numbers of total immunoglobulin (Ig)-secreting cells, with predominance of IgG2a-producing cells; and (vi) increased production of gamma interferon and interleukin 4. In addition, these mice presented lower IgM and higher IgG2a and IgG1 parasite-specific serum antibody levels. Our results indicate that the parasite load at the acute phase of T. cruzi infection influences the activation of the immune system and development of Chagas’ disease pathology at the late chronic phase of the disease.

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Dynamics of T Cells Repertoire During Trypanosoma cruzi Infection and its Post-Treatment Modulation

Current Medicinal Chemistry ◽

10.2174/0929867325666181101111819 ◽

2019 ◽

Vol 26 (36) ◽

pp. 6519-6543 ◽

Cited By ~ 1

Author(s):

Adriana Egui ◽

Paola Lasso ◽

Elena Pérez-Antón ◽

M. Carmen Thomas ◽

Manuel Carlos López

Keyword(s):

Immune Response ◽

Trypanosoma Cruzi ◽

Chagas Disease ◽

Cardiac Tissue ◽

Acute Infection ◽

Clinical Status ◽

Chronic Phase ◽

Parasite Load ◽

Chronic Patients ◽

Cruzi Infection

Chagas disease courses with different clinical phases and has a variable clinical presentation and progression. The acute infection phase mostly exhibits a non-specific symptomatology. In the absence of treatment, the acute phase is followed by a chronic phase, which is initially asymptomatic. This chronic asymptomatic phase of the disease is characterized by a fragile balance between the host’s immune response and the parasite replication. The loss of this balance is crucial for the progression of the sickness. The virulence and tropism of the T. cruzi infecting strain together to the inflammation processes in the cardiac tissue are the main factors for the establishment and severity of the cardiomyopathy. The efficacy of treatment in chronic Chagas disease patients is controversial. However, several studies carried out in chronic patients demonstrated that antiparasitic treatment reduces parasite load in the bloodstream and leads to an improvement in the immune response against the Trypanosoma cruzi parasite. The present review is mainly focused on the cellular patterns associated to the clinical status and the evolution of the disease in chronic patients, as well as the effectiveness of the treatment related to T. cruzi infection control. Therefore, an emphasis is placed on the dynamics of specific-antigens T cell subpopulations, their memory and activation phenotypes, their functionality and their contribution to pathogenesis or disease control, as well as their association with risk of congenital transmission of the parasite.

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Evolution of subpatent parasitaemia in Trypanosoma cruzi chronically infected mice with the help of a cyclophosphamide amplification transfer assay

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46651991000600013 ◽

1991 ◽

Vol 33 (6) ◽

pp. 509-514 ◽

Cited By ~ 1

Author(s):

José M. Alvarez ◽

Ayumi Oshima ◽

Veronica Mozer ◽

Liliane Guimarães ◽

Hércules Menezes

Keyword(s):

Trypanosoma Cruzi ◽

Acute Phase ◽

Chronic Phase ◽

Detection Tool ◽

Highly Sensitive ◽

Parasite Detection ◽

Cyclophosphamide Treatment ◽

One Year ◽

Cruzi Infection

We have evaluated the sensitivity of the classical blood subinoculation method, modified through cyclophosphamide treatment of transferred mice, for the detection of occult parasitaemias in Trypanosoma cruzi chronically infected mice. Besides its simplicity, the method was shown to be highly sensitive for both the "chronic" phase parasites (99% of chronic cases were shown to harbour occult parasitaemias) and for the acute phase parasites (T. cruzi could be detected in 53.8% of animals transferred with one Y strain parasite and in 20% of animals transferred with one CL strain parasite). Using acute phase bloodforms, the assay proved to be more sensitive than conventional subinoculation when dealing with the CL, but not the Y strain of the parasite. With the help of this parasite detection tool, we have studied during a one year period, the evolution of subpatent parasitaemias in a group of mice which survived through chemotherapy from lethal acute phase of T. cruzi infection. Cyclophosphamide transfer assay revealed occult parasitaemias in 100% of the chronic animals, nevertheless, continuous and discontinuous patterns of positivity were observed.

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Temporal Distribution and Parasite Load Kinetics in Blood and Tissues during Neospora caninum Infection in Mice

Infection and Immunity ◽

10.1128/iai.74.4.2491-2494.2006 ◽

2006 ◽

Vol 74 (4) ◽

pp. 2491-2494 ◽

Cited By ~ 54

Author(s):

Esther Collantes-Fernández ◽

Inmaculada López-Pérez ◽

Gema Álvarez-García ◽

Luis M. Ortega-Mora

Keyword(s):

Acute Phase ◽

Neospora Caninum ◽

Clinical Signs ◽

Chronic Phase ◽

Temporal Distribution ◽

Parasite Load ◽

Caninum Infection ◽

Kinetics Of ◽

The Brain

ABSTRACT The kinetics of Neospora caninum loads in mice inoculated with NC-Liv or NC-1 isolates were studied. The acute phase was characterized by parasitemia and the detection of parasite DNA in several organs, whereas during the chronic phase, the parasite was detected mainly in the brain. Mice infected with NC-Liv developed clinical signs, showing higher brain parasite burdens than NC-1-infected mice.

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Aspirin-triggered resolvin D1 reduces parasitic cardiac load by decreasing inflammation through N-formyl peptide receptor 2 in a chronic murine model of Chagas disease

10.1101/2021.08.17.456695 ◽

2021 ◽

Author(s):

Ileana Carrillo ◽

Rayane Rabelo ◽

Cesar Barbosa ◽

Mariana Rates ◽

Sebasti&aacuten Fuentes-Retamal ◽

...

Keyword(s):

Inflammatory Response ◽

Chagas Disease ◽

Cardiac Tissue ◽

Chronic Phase ◽

Parasite Load ◽

Formyl Peptide Receptor ◽

Resolvin D1 ◽

Peptide Receptor ◽

Formyl Peptide ◽

Cruzi Infection

Chagas disease, caused by the protozoan Trypanosoma cruzi, is endemic in Latin America and is widely distributed worldwide because of migration. After years of infection and in the absence of treatment, the disease progresses from an acute and asymptomatic phase to a chronic inflammatory cardiomyopathy, leading to heart failure and death. An inadequate balance in the inflammatory response is involved in the progression of chronic Chagas cardiomyopathy. Current therapeutic strategies cannot prevent or reverse the heart damage caused by the parasite. Aspirin-triggered resolvin D1 (AT-RvD1) is a pro-resolving mediator of inflammation that acts through N-formyl peptide receptor 2 (FPR2). AT-RvD1 participates in the modification of cytokine production, inhibition of leukocyte recruitment and efferocytosis, macrophage switching to a nonphlogistic phenotype, and the promotion of healing, thus restoring organ function. In the present study, AT-RvD1 is proposed as a potential therapy aid to regulate the pro-inflammatory state during the chronic phase of Chagas disease. C57BL/6 wild-type and FPR2 knock-out mice chronically infected with T. cruzi were treated for 20 days with 5 μg/kg/day AT-RvD1, 30 mg/kg/day benznidazole, or the combination of 5 μg/kg/day AT-RvD1 and 5 mg/kg/day benznidazole. At the end of treatment, changes in the immune response, cardiac tissue damage, and parasite load were evaluated. The administration of AT-RvD1 in the chronic phase of T. cruzi infection regulated the inflammatory response both at the systemic level and in the cardiac tissue, and it reduced cellular infiltrates, cardiomyocyte hypertrophy, fibrosis, and the parasite load in the heart tissue. Thus, AT-RvD1 was shown to be an attractive therapeutic due to its regulatory effect on the inflammatory response at the cardiac level and its ability to reduce the parasite load during chronic T. cruzi infection, thereby preventing the chronic cardiac damage induced by the parasite.

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The hamster (mesocricetus auratus) as experimental model in chagas' disease: parasitological and histopathological studies in acute and chronic phases of Trypanosoma cruzi infection

Revista da Sociedade Brasileira de Medicina Tropical ◽

10.1590/s0037-86821994000300007 ◽

1994 ◽

Vol 27 (3) ◽

pp. 163-169 ◽

Cited By ~ 24

Author(s):

Luis Eduardo Ramirez ◽

Eliane Lages-Silva ◽

José Maria Soares Junior ◽

Edmundo Chapadeiro

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Smooth Muscle ◽

Chagas Disease ◽

Acute Phase ◽

Chronic Phase ◽

Variable Degree ◽

Leukocyte Infiltration ◽

Histopathological Studies ◽

Cruzi Infection

This research characterizes the acute and chronic phases of Chagas ' disease in hamster through parasitological and histopathological studies. The acute phase was achieved with 44 young hamsters injected intraperitoneally with 100.000 blood trypomastigotes of Benedito and Y strains of T. cruzi. The chronic phase was induced in 46 hamsters injected intraperitoneally with 35.000 trypomastigotes ofVicentina, Benedito and Y strains. Animals were sacrificed at regular intervals of 24 hours of acute phase and from the 3rd to the 10th month of infection ofchronic phase. In the acute phase, parasites were easily recoveredfrom all animals and there was an inflammatory reaction characterized by mononuclear and polymorphous leukocyte infiltration of variable degree in the majority of tissues and organs, specially in the connective loose and fatty tissues, smooth muscle myocardium and skeletal muscle. In the chronic phase the lesions occurred in the same tissues and organs, but the inflammatory response was less severe and characterized by mononuclear infiltration mainly with focal or zonalfibrosis in the myocardiun. In 50% of infected animals parasites were found inmyocardiun and recoveredfrom pericardic, peritoneal and ascitic fluids in some animals. Signs of heart failure, sudden death and enlargement of bowel were observed regularly. We concluded that the hamster is an useful model for Chagas' disease studies.

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Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis using Q-PCR

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01323-16 ◽

2016 ◽

pp. AAC.01323-16 ◽

Cited By ~ 2

Author(s):

Mahbobeh Montazeri ◽

Mohammad Ali Ebrahimzadeh ◽

Ehsan Ahmadpour ◽

Mehdi Sharif ◽

Shahabeddin Sarvi ◽

...

Keyword(s):

Treatment Group ◽

Side Effects ◽

Acute Phase ◽

Chronic Phase ◽

Parasite Load ◽

Post Treatment ◽

Low Doses ◽

Current Therapies ◽

Pre Treatment

Current therapies against toxoplasmosis are limited and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasmaactivity of propranolol 2, 3 mg/kg/dayin vivoin acute and chronic phases. Propranolol as the stabilizing cell membrane is a suitable drug for inhibiting the entrance ofToxoplasma gondii(T. gondii) tachyzoites into cells. The acute phase was performed using propranolol, pyrimethamine, propranolol plus pyrimethamine before (pre-treatment) and after (post-treatment) intraperitoneally challenge with 1×103tachyzoites of the virulent RH strain ofT. gondiiin Balb/c mice. Also in the chronic phase, treatment was performed 12 hours before intraperitoneally challenge with 1×106tachyzoites of the virulent RH strain ofT. gondiiin rats. One week (in acute phase) and two months (in chronic phase) after post infection, tissues were isolated and DNA was extracted. Subsequently parasite load was calculated using Q-PCR. In acute phase, in both groups, significant anti-Toxoplasmaactivity was observed using propranolol (P< 0.001). Propranolol in pre-treatment group showed higher anti-Toxoplasmaactivity than propranolol in post-treatment in brain tissues displaying therapeutic efficiency on toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in pre-treatment group. In the chronic phase, anti-Toxoplasmaactivity was observed with propranolol and decreased parasite load in tissues. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective against acute and latent murine toxoplasmosis at low doses and increase efficiency of drug in combination therapy with propranolol-pyrimethamine.

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Pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection

10.1101/175646 ◽

2017 ◽

Author(s):

Adam L. Bailey ◽

Connor R. Buechler ◽

Daniel R. Matson ◽

Eric J. Peterson ◽

Kevin G. Brunner ◽

...

Keyword(s):

Immune System ◽

Hiv Infection ◽

Protective Effect ◽

Acute Phase ◽

Human Population ◽

Chronic Phase ◽

Immune Recognition ◽

Irreversible Damage ◽

Macaque Model ◽

High Prevalence

AbstractHuman pegivirus (HPgV) protects HIV+ people from HIV-associated disease, but the mechanism of this protective effect remains poorly understood. We sequentially infected cynomolgus macaques with simian pegivirus (SPgV) and simian immunodeficiency virus (SIV) to model HIV+HPgV co-infection. SPgV had no effect on acute-phase SIV pathogenesis – as measured by SIV viral load, CD4+ T cell destruction, and immune activation – suggesting that HPgV’s protective effect is exerted primarily during the chronic phase of HIV infection. We also examined the immune response to SPgV in unprecedented detail, and found that this virus elicits virtually no activation of the immune system despite persistently high titers in the blood over long periods of time. Overall, this study expands our understanding of the pegiviruses – an understudied group of viruses with a high prevalence in the global human population – and suggests that the protective effect observed in HIV+HPgV co-infected people occurs primarily during the chronic phase of HIV infection.One Sentence SummaryPegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection.Short TitlePegivirus and AIDS-virus co-infectionAccessible SummaryPeople infected with HIV live longer, healthier lives when they are co-infected with the human pegivirus (HPgV) – an understudied virus with a high prevalence in the global human population. To better understand how HPgV protects people with HIV from HIV-associated disease, we infected macaques with simian versions of these two viruses (SPgV and SIV). We found that SPgV had no impact on the incidence of SIV-associated disease early during the course of SIV infection – a time when SIV and HIV are known to cause irreversible damage to the immune system. Oddly, we found that the immune system did not recognize SPgV; a finding that warrants further investigation. Overall, this study greatly expands on our understanding of the pegiviruses and their interaction with the immune system.

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SNI and CFA induce similar changes in TRPV1 and P2X3 expressions in the acute phase but not in the chronic phase of pain

Experimental Brain Research ◽

10.1007/s00221-020-05988-4 ◽

2021 ◽

Author(s):

Junfan Fang ◽

Junying Du ◽

Xuaner Xiang ◽

Xiaomei Shao ◽

Xiaofeng He ◽

...

Keyword(s):

Acute Phase ◽

Chronic Phase

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