IL-4 reduces resistance of mice to Trypanosoma cruzi infection

Hiyama, K; Hamano, Shinjiro; Nakamura, Takahiko; Nomoto, Kikuo; Tada, Isao

doi:10.1007/pl00008577

Cited by 26 publications

(19 citation statements)

References 13 publications

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“…Mice that are genetically deficient in or treated with monoclonal antibodies against the Th1 cytokines interferon (IFN)-␥, interleukin (IL)-12, and tumor necrosis factor (TNF)-␣ have reduced heart inflammation during T. cruzi-induced myocarditis [15][16][17]. Conversely, the Th2 cytokines IL-10, transforming growth factor-␤, and IL-4 downregulate the immune response and prevent potential tissue damage to the host [15,18,19]. Interestingly, MMP-2 and MMP-9 have been shown to be important modulators of immune responses.…”

Section: Chagasic Cardiomyopathy Triggered By Infection Withmentioning

confidence: 99%

Increased Activities of Cardiac Matrix Metalloproteinases Matrix Metalloproteinase (MMP)–2 and MMP‐9 Are Associated with Mortality during the Acute Phase of ExperimentalTrypanosoma cruziInfection

Gutierrez

Lalu

Mariano³

et al. 2008

J INFECT DIS

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The strong inflammatory reaction that occurs in the heart during the acute phase of Trypanosoma cruzi infection is modulated by cytokines and chemokines produced by leukocytes and cardiomyocytes. Matrix metalloproteinases (MMPs) have recently emerged as modulators of cardiovascular inflammation. In the present study we investigated the role of MMP-2 and MMP-9 in T. cruzi-induced myocarditis, by use of immunohistochemical analysis, gelatin zymography, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction to analyze the cardiac tissues of T. cruzi-infected C57BL/6 mice. Increased transcripts levels, immunoreactivity, and enzymatic activity for MMP-2 and MMP-9 were observed by day 14 after infection. Mice treated with an MMP inhibitor showed significantly decreased heart inflammation, delayed peak in parasitemia, and improved survival rates, compared with the control group. Reduced levels of cardiac tumor necrosis factor-alpha, interferon-gamma, serum nitrite, and serum nitrate were also observed in the treated group. These results suggest an important role for MMPs in the induction of T. cruzi-induced acute myocarditis.

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Section: Chagasic Cardiomyopathy Triggered By Infection Withmentioning

confidence: 99%

Increased Activities of Cardiac Matrix Metalloproteinases Matrix Metalloproteinase (MMP)–2 and MMP‐9 Are Associated with Mortality during the Acute Phase of ExperimentalTrypanosoma cruziInfection

Gutierrez

Lalu

Mariano³

et al. 2008

J INFECT DIS

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“…TNF- α has also been associated with macrophage activation as a secondary signal for nitric oxide production [10]. In contrast, cytokines such as IL-4 and TGF- β are associated with parasite susceptibility [11], [12].…”

Section: Introductionmentioning

confidence: 99%

IFN-γ Plays a Unique Role in Protection against Low Virulent Trypanosoma cruzi Strain

et al. 2012

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Background T. cruzi strains have been divided into six discrete typing units (DTUs) according to their genetic background. These groups are designated T. cruzi I to VI. In this context, amastigotes from G strain ( T. cruzi I) are highly infective in vitro and show no parasitemia in vivo . Here we aimed to understand why amastigotes from G strain are highly infective in vitro and do not contribute for a patent in vivo infection. Methodology/Principal Findings Our in vitro studies demonstrated the first evidence that IFN-γ would be associated to the low virulence of G strain in vivo . After intraperitoneal amastigotes inoculation in wild-type and knockout mice for TNF-α, Nod2, Myd88, iNOS, IL-12p40, IL-18, CD4, CD8 and IFN-γ we found that the latter is crucial for controlling infection by G strain amastigotes. Conclusions/Significance Our results showed that amastigotes from G strain are highly infective in vitro but did not contribute for a patent infection in vivo due to its susceptibility to IFN-γ production by host immune cells. These data are useful to understand the mechanisms underlying the contrasting behavior of different T. cruzi groups for in vitro and in vivo infection.

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“…Hemin was replaced by hemoglobin (Japan Biotest Intitute). The trypomastigotes were harvested from the culture supernatant of rhesus monkey kidney (LLC-MK2) cells infected with T. cruzi (Hiyama et al 2001). LLC-MK2 cells were maintained in Dulbecco's modified Eagle's medium (DMEM, Sigma) containing 10% fetal bovine serum (FBS, Gibco).…”

Section: Cultivation Of T Cruzi -mentioning

confidence: 99%

Trypanocidal constituents in plants: 7. Mammea-type coumarins

Reyes-Chilpa

Estrada-Muñiz

Vega-Ávila

et al. 2008

Mem. Inst. Oswaldo Cruz

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The protozoan Trypanosoma cruzi is the etiological agent of Chagas disease (American trypanosomiasis), which affects 16-18 million people in Latin America and is responsible for the deaths of more than 45,000 patients per year (WHO 1997). It is transmitted to humans by triatomine bugs or through infected blood transfusions (Pizzolatti et al. 2002). The life cycle of T. cruzi is complex, and it alternates between vertebrate and invertebrate hosts. When the triatomine bug is feeding on human blood, it defecates and releases metacyclic trypomastigotes near the bite wound. This infective agent is capable of reaching intracellular locations and transforming into amastigotes. After reproduction, the amastigotes turn back into trypomastigotes, and the cells burst. The released parasites can either infect other cells or be consumed by other triatomine bugs. In the intestine of an invertebrate host, the blood trypomastigotes transform into epimastigotes, which divide and give rise to infective metacyclic-trypomastigotes (Brener 1973, Contreras et al. 2002.Medication for Chagas disease is usually effective when given during the acute stage of infection. Once the disease has progressed to later stages, no medication has proven to be completely effective. Moreover, synthetic drugs such as nifurtimox, a 5-nitrofuran, and benznidazole, a 2-nitro-imidazole (Lampit®, Bayer, and Rochagan®, Roche, respectively) are used for the treatment of this disease. Unfortunately, both drugs have limited efficacy during the chronic phase of the disease and present several undesirable side effects (Gutteridge 1985, Umezawa et al. 2001, Coura & Castro 2002. Chemoprophylatic measures against Chagas disease are scarce, present variable efficacy, or are not adopted due to their costs. Currently, gentian violet is used to sterilize blood banks in endemic areas (Pizzolatti et al. 2002, Coura & Castro 2002). An urgent need to develop new drugs exists, and natural products can provide useful drug leads as well as the scientific basis for the rational use of medicinal plants.Calophyllum brasiliense Camb. is a large tree, measuring up to 40 m in height, from the tropical rain forest. It is distributed throughout Latin America, from Brazil to Mexico, and is used in folk medicine. In Mexico, its most common name is bari, and the infusion of the cortex is consumed by women over nine days for "cleaning" the womb after child-birth, while the seeds provide an oil used for lighting and for healing skin afflictions (Soto & Sousa 1995). In Colombia, the peasants call this tree ár-bol de aceite (oil tree), and the yellow latex exuded from the cortex is applied topically for healing the navels of newborn children (García-Barriga 1992). In Brazil, it is known as guanandi, and has been used in folk medicine for the treatment of rheumatism, varicose hemorrhoids and chronic ulcers (Corrêa 1978). In the Amazon basin, the bark infusion is used by the Karaja ethnic group for the treatment of diarrhea, and in Guyana, C. brasiliense is mixed with Coutarea hexandra to trea...

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IL-4 reduces resistance of mice to Trypanosoma cruzi infection

Cited by 26 publications

References 13 publications

Increased Activities of Cardiac Matrix Metalloproteinases Matrix Metalloproteinase (MMP)–2 and MMP‐9 Are Associated with Mortality during the Acute Phase of ExperimentalTrypanosoma cruziInfection

Increased Activities of Cardiac Matrix Metalloproteinases Matrix Metalloproteinase (MMP)–2 and MMP‐9 Are Associated with Mortality during the Acute Phase of ExperimentalTrypanosoma cruziInfection

IFN-γ Plays a Unique Role in Protection against Low Virulent Trypanosoma cruzi Strain

Trypanocidal constituents in plants: 7. Mammea-type coumarins

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