scholarly journals Modulation of Autoimmunity by Treatment of an Infectious Disease

2007 ◽  
Vol 75 (7) ◽  
pp. 3641-3650 ◽  
Author(s):  
Kenneth V. Hyland ◽  
Juan S. Leon ◽  
Melvin D. Daniels ◽  
Nick Giafis ◽  
LaKitta M. Woods ◽  
...  
Keyword(s):  
Central America ◽  
Antibody Production ◽  
Virulent Strain ◽  
Chronic Phase ◽  
Parasite Load ◽  
Autoimmune Response ◽  
Delayed Type Hypersensitivity ◽  
Cardiac Myosin ◽  
Chagas Heart Disease ◽  
Brazil Strain

ABSTRACT Chagas’ heart disease (CHD), caused by the parasite Trypanosoma cruzi, is the most common form of myocarditis in Central America and South America. Some humans and experimental animals develop both humoral and cell-mediated cardiac-specific autoimmunity during infection. Benznidazole, a trypanocidal drug, is effective at reducing parasite load and decreasing the severity of myocarditis in acutely infected patients. We hypothesized that the magnitude of autoimmunity that develops following T. cruzi infection is directly proportional to the amount of damage caused by the parasite. To test this hypothesis, we used benznidazole to reduce the number of parasites in an experimental model of CHD and determined whether this treatment altered the autoimmune response. Infection of A/J mice with the Brazil strain of T. cruzi leads to the development of severe inflammation, fibrosis, necrosis, and parasitosis in the heart accompanied by vigorous cardiac myosin-specific delayed-type hypersensitivity (DTH) and antibody production at 21 days postinfection. Mice succumbed to infection within a month if left untreated. Treatment of infected mice with benznidazole eliminated mortality and decreased disease severity. Treatment also reduced cardiac myosin-specific DTH and antibody production. Reinfection of treated mice with a heart-derived, virulent strain of T. cruzi or immunization with myosin led to the redevelopment of myosin-specific autoimmune responses and inflammation. These results provide a direct link between the levels of T. cruzi and the presence of autoimmunity and suggest that elimination of the parasite may result in the reduction or elimination of autoimmunity in the chronic phase of infection.

scholarly journals Cardiac Myosin Autoimmunity in Acute Chagas' Heart Disease

2001 ◽  
Vol 69 (9) ◽  
pp. 5643-5649 ◽  
Author(s):  
Juan S. Leon ◽  
Lisa M. Godsel ◽  
Kegiang Wang ◽  
David M. Engman
Keyword(s):  
Chronic Phase ◽  
Delayed Type Hypersensitivity ◽  
Cardiac Myosin ◽  
Susceptible Host ◽  
Specific Antibodies ◽  
Chagas Heart Disease ◽  
Brazil Strain ◽  
Low Levels ◽  
Stimulation Of

ABSTRACT Infection with Trypanosoma cruzi, the agent of Chagas' disease, may induce antibodies and T cells reactive with self antigens (autoimmunity). Because autoimmunity is generally thought to develop during the chronic phase of infection, one hypothesis is that autoimmunity develops only after long-term, low-level stimulation of self-reactive cells. However, preliminary reports suggest that autoimmunity may begin during acute T. cruzi infection. The goal of the present study was to investigate whether cardiac autoimmunity could be observed during acute T. cruziinfection. A/J mice infected with the Brazil strain of T. cruzi for 21 days developed severe myocarditis, accompanied by humoral and cellular autoimmunity. Specifically, T. cruziinfection induced immunoglobulin G (IgG) autoantibodies and delayed type hypersensitivity (DTH) to cardiac myosin. This autoimmunity resembles that which develops in A/J mice immunized with myosin in complete Freund's adjuvant in that myosin-specific antibodies and DTH responses both develop by 21 days postinfection or postimmunization. While the levels of myosin IgG in T. cruzi-infected mice were slightly lower than those in myosin-immunized mice, the magnitude of myosin DTH in the two groups was statistically equivalent. In contrast, C57BL/6 mice, which are resistant to myosin-induced myocarditis and its associated autoimmunity, developed undetectable or low levels of myosin IgG and did not exhibit myosin DTH or myocarditis upon T. cruzi infection. Therefore, humoral and cellular cardiac autoimmunity can develop during acute T. cruziinfection in the genetically susceptible host.

scholarly journals A Cardiac Myosin-Specific Autoimmune Response Is Induced by Immunization with Trypanosoma cruzi Proteins

2004 ◽  
Vol 72 (6) ◽  
pp. 3410-3417 ◽  
Author(s):  
Juan S. Leon ◽  
Melvin D. Daniels ◽  
Krista M. Toriello ◽  
Kegiang Wang ◽  
David M. Engman
Keyword(s):  
Trypanosoma Cruzi ◽  
Protozoan Parasite ◽  
Autoimmune Response ◽  
Delayed Type Hypersensitivity ◽  
Cardiac Myosin ◽  
Cardiac Damage ◽  
Cardiac Inflammation ◽  
Skeletal Myosin ◽  
Chagas Heart Disease ◽  
Fatal Cardiomyopathy

ABSTRACT Trypanosoma cruzi is the protozoan parasite that causes Chagas' heart disease, a potentially fatal cardiomyopathy prevalent in Central and South America. Infection with T. cruzi induces cardiac myosin autoimmunity in susceptible humans and mice, and this autoimmunity has been suggested to contribute to cardiac inflammation. To address how T. cruzi induces cardiac myosin autoimmunity, we investigated whether immunity to T. cruzi antigens could induce cardiac myosin-specific autoimmunity in the absence of live parasites. We immunized A/J mice with a T. cruzi Brazil-derived protein extract emulsified in complete Freund's adjuvant and found that these mice developed cardiac myosin-specific delayed-type hypersensitivity (DTH) and autoantibodies in the absence of detectable cardiac damage. The induction of autoimmunity was specific since immunization with extracts of the related protozoan parasite Leishmania amazonensis did not induce myosin autoimmunity. The immunogenetic makeup of the host was important for this response, since C57BL/6 mice did not develop cardiac myosin DTH upon immunization with T. cruzi extract. Perhaps more interesting, mice immunized with cardiac myosin developed T. cruzi-specific DTH and antibodies. This DTH was also antigen specific, since immunization with skeletal myosin and myoglobin did not induce T. cruzi-specific immunity. These results suggest that immunization with cardiac myosin or T. cruzi antigen can induce specific, bidirectionally cross-reactive immune responses in the absence of detectable cardiac damage.

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

2019 ◽  
Vol 26 (36) ◽  
pp. 6519-6543 ◽  
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.

scholarly journals Chagas Disease Serological Test Performance in U.S. Blood Donor Specimens

2019 ◽  
Vol 57 (12) ◽  
Author(s):  
Jeffrey D. Whitman ◽  
Christina A. Bulman ◽  
Emma L. Gunderson ◽  
Amanda M. Irish ◽  
Rebecca L. Townsend ◽  
...  
Keyword(s):  
United States ◽  
South America ◽  
Central America ◽  
Chagas Disease ◽  
Blood Donor ◽  
Test Performance ◽  
Chronic Phase ◽  
High Specificity ◽  
The United States ◽  
Confirmatory Test

ABSTRACT Chagas disease affects an estimated 300,000 individuals in the United States. Diagnosis in the chronic phase requires positive results from two different IgG serological tests. Three enzyme-linked immunosorbent assays (ELISAs) (Hemagen, Ortho, and Wiener) and one rapid test (InBios) are FDA cleared, but comparative data in U.S. populations are sparse. We evaluated 500 seropositive and 300 seronegative blood donor plasma samples. Country of birth was known for 255 seropositive specimens, which were grouped into regions as follows: Mexico (n = 94), Central America (n = 88), and South America (n = 73). Specimens were tested by the four FDA-cleared IgG serological assays. Test performance was evaluated by two comparators and latent class analysis. InBios had the highest sensitivity (97.4% to 99.3%) but the lowest specificity (87.5% to 92.3%). Hemagen had the lowest sensitivity (88.0% to 92.0%) but high specificity (99.0% to 100.0%). The level of sensitivity was intermediate for Ortho (92.4% to 96.5%) and Wiener (94.0% to 97.1%); both had high specificity (98.8% to 100.0% and 96.7% to 99.3%, respectively). The levels of antibody reactivity and clinical sensitivity were lowest in donors from Mexico, intermediate in those from Central America, and highest in those from South America. Our findings provide an initial evidence base to improve laboratory diagnosis of Chagas disease in the United States. The best current testing algorithm would employ a high-sensitivity screening test followed by a high-specificity confirmatory test.

An IL-2–toxin, DAB389 IL-2, inhibits delayed-type hypersensitivity but enhances IgE antibody production

1999 ◽  
Vol 103 (5) ◽  
pp. 843-849 ◽  
Author(s):  
Teet Pullerits ◽  
Samuel Lundin ◽  
Ulf Dahlgren ◽  
Esbjörn Telemo ◽  
Lars Åke Hanson ◽  
...  
Keyword(s):  
Antibody Production ◽  
Delayed Type Hypersensitivity ◽  
Ige Antibody

scholarly journals Influence of Acute-Phase Parasite Load on Pathology, Parasitism, and Activation of the Immune System at the Late Chronic Phase of Chagas’ Disease

1999 ◽  
Vol 67 (1) ◽  
pp. 308-318 ◽  
Author(s):  
Claudio R. F. Marinho ◽  
Maria Regina D’Império Lima ◽  
Marcos G. Grisotto ◽  
José M. Alvarez
Keyword(s):  
Immune System ◽  
Chagas Disease ◽  
Acute Phase ◽  
Serum Antibody ◽  
Chronic Phase ◽  
Parasite Load ◽  
Interleukin 4 ◽  
High Dose ◽  
Macrophage Phenotype ◽  
High Parasite

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.

Delayed Hypersensitivity to Toxoplasma and Unrelated Antigens in Toxoplasma -Infected Mice: Induction and Elicitation of Delayed-Type Hypersensitivity by Antigen-Pulsed Macrophages

1980 ◽  
Vol 28 (2) ◽  
pp. 524-531 ◽  
Author(s):  
Emanuela Handman ◽  
Patrice M. Chester ◽  
Jack S. Remington
Keyword(s):  
T Cells ◽  
Antibody Response ◽  
Chronic Infection ◽  
Chronic Phase ◽  
Keyhole Limpet Hemocyanin ◽  
Delayed Type Hypersensitivity ◽  
Intracellular Parasites ◽  
Infected Cells ◽  
Uptake Method ◽  
Formalin Fixed

Delayed-type hypersensitivity (DTH) to Toxoplasma and unrelated antigens in Toxoplasma -infected BALB/c mice was investigated by the radioisotopic uptake method of Vadas et al. (Int. Arch. Allergy Appl. Immunol. 49: 670-692, 1975). DTH became positive on day 30 of infection and remained positive during chronic infection. The expression of DTH in mice infected with the relatively avirulent C37 strain of the parasite paralleled the Toxoplasma antibody response as detected by the Sabin-Feldman dye test. Mice sensitized with Toxoplasma , keyhole limpet hemocyanin, or sheep erythrocytes during the acute or chronic phase of Toxoplasma infection showed a DTH reaction similar to that of uninfected sensitized controls. No parasite antigens could be detected by immunofluorescence techniques on the surface of Toxoplasma -infected cells. When killed organisms were added to the cell cultures, specks of fluorescence appeared on cells containing intracellular parasites as well as on cells without intracellular organisms. That the antigens may be present in or on macrophages in a form readily recognizable by T cells is suggested by experiments in which we demonstrated that injection of uninfected normal macrophages pulsed with Toxoplasma -soluble antigens into the ears of chronically infected mice elicited a DTH reaction comparable to that observed when 10 6 Formalin-fixed tachyzoites were used as the test antigen. When macrophages pulsed with Toxoplasma antigen were used in attempts to induce DTH in naive uninfected mice, the intensity of the reaction was similar to that observed in infected mice.

scholarly journals Detection of circulating polysaccharide antigen of Schistosoma mansoni in hamster sera by crossed immunoelectrophoresis

1988 ◽  
Vol 30 (2) ◽  
pp. 72-78
Author(s):  
Margareth Fernandes ◽  
Ione Irulegui ◽  
Dirce Mary Correia Lima ◽  
Clarice Pires Abrantes ◽  
Martha Smith Cressoni ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Chronic Phase ◽  
Parasite Load ◽  
Polysaccharide Antigen ◽  
Experimental Conditions ◽  
Crossed Immunoelectrophoresis ◽  
Human Sera

Crossed immunoelectrophoresis (IEC) was used for detection of free and complexed circulating polisaccharide anodic antigen (AgCA) of Schistosoma mansoni in sera of infected hamsters. An attempt was also done to detect AgCA in human sera from patients infected with S. mansoni. The conditions for isolation and detection of complexed AgCA were established. The sensitivity of IEC was increased by incorporation of 2% polyethylene glicol (PEG) to the agarose and by maintaining the system at 4°C during the electrophoretic run. Free AgCA was detected in 12 and the complexed in 30 of the 37 hamsters sera analysed. Correlation between AgCA (free and complexed) and the parasite load was observed. AgCA was not detected, under the experimental conditions used, in human sera from 7 patients in the acute and 23 in the chronic phase of infection.

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