The endless race betweenTrypanosoma cruziand host immunity: lessons for and beyond Chagas disease

2010 ◽  
Vol 12 ◽  
Author(s):  
Caroline Junqueira ◽  
Braulia Caetano ◽  
Daniella C. Bartholomeu ◽  
Mariane B. Melo ◽  
Catherine Ropert ◽  
...  
Keyword(s):  
T Cell ◽  
Chagas Disease ◽  
Protozoan Parasite ◽  
Genetically Engineered ◽  
Disease Outcome ◽  
Host Responses ◽  
Cell Mediated Immunity ◽  
Cell Responses ◽  
Host Parasite

Infection with the protozoan parasiteTrypanosoma cruzi, the agent of Chagas disease, is characterised by a variable clinical course – from symptomless cases to severe chronic disease with cardiac and/or gastrointestinal involvement. The variability in disease outcome has been attributed to host responses as well as parasite heterogeneity. In this article, we review studies indicating the importance of immune responses as key determinants of host resistance toT. cruziinfection and the pathogenesis of Chagas disease. Particular attention is given to recent studies defining the role of cognate innate immune receptors and immunodominant CD8+T cells that recognise parasite components – both crucial for host–parasite interaction and disease outcome. In light of these studies we speculate about parasite strategies that induce a strong and long-lasting T-cell-mediated immunity but at the same time allow persistence of the parasite in the vertebrate host. We also discuss what we have learned from these studies for increasing our understanding of Chagas pathogenesis and for the design of new strategies to prevent the development of Chagas disease. Finally, we highlight recent studies employing a genetically engineered attenuatedT. cruzistrain as a vaccine shuttle that elicits potent T cell responses specific to a tumour antigen and protective immunity against a syngeneic melanoma cell line.

scholarly journals R-Ras is required for murine dendritic cell maturation and CD4+ T-cell priming

Blood ◽  
2012 ◽  
Vol 119 (7) ◽  
pp. 1693-1701 ◽  
Author(s):  
Gobind Singh ◽  
Daigo Hashimoto ◽  
Xiaocai Yan ◽  
Julie Helft ◽  
Patricia J.-Y. Park ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Dendritic Cell Maturation ◽  
Cell Mediated Immunity ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Cell Responses ◽  
Small G Protein ◽  
Physiologic Function

Abstract R-Ras is a member of the RAS superfamily of small GTP-binding proteins. The physiologic function of R-Ras has not been fully elucidated. We found that R-Ras is expressed by lymphoid and nonlymphoid tissues and drastically up-regulated when bone marrow progenitors are induced to differentiate into dendritic cells (DCs). To address the role of R-Ras in DC functions, we generated a R-Ras-deficient mouse strain. We found that tumors induced in Rras−/− mice formed with shorter latency and attained greater tumor volumes. This finding has prompted the investigation of a role for R-Ras in the immune system. Indeed, Rras−/− mice were impaired in their ability to prime allogeneic and antigen-specific T-cell responses. Rras−/− DCs expressed lower levels of surface MHC class II and CD86 in response to lipopolysaccharide compared with wild-type DCs. This was correlated with a reduced phosphorylation of p38 and Akt. Consistently, R-Ras–GTP level was increased within 10 minutes of lipopolysaccharide stimulation. Furthermore, Rras−/− DCs have attenuated capacity to spread on fibronectin and form stable immunologic synapses with T cells. Altogether, these findings provide the first demonstration of a role for R-Ras in cell-mediated immunity and further expand on the complexity of small G-protein signaling in DCs.

scholarly journals T cell–specific STAT3 deficiency abrogates lupus nephritis

Lupus ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 1468-1472 ◽  
Author(s):  
N Yoshida ◽  
F He ◽  
V C Kyttaris
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Cell Responses ◽  
Cytokines And Chemokines ◽  
Novel Approach ◽  
Cell Tissue ◽  
External Stimuli

Signal transducer and activator of transcription (STAT) 3 is a regulator of T-cell responses to external stimuli, such as pro-inflammatory cytokines and chemokines. We have previously shown that STAT3 is activated (phosphorylated) at high levels in systemic lupus erythematosus (SLE) T cells and mediates chemokine-induced migration and T:B cell interactions. Stattic, a small molecular STAT3 inhibitor, can partially ameliorate lupus nephritis in mice. To understand the role of STAT3 better in T-cell pathophysiology in lupus nephritis and its potential as a treatment target, we silenced its expression in T cells using a cd4-driven CRE-Flox model. We found that lupus-prone mice that do not express STAT3 in T cells did not develop lymphadenopathy, splenomegaly, or glomerulonephritis. Moreover, the production of anti-dsDNA antibodies was decreased in these mice compared to controls. To dissect the mechanism, we also used a nephrotoxic serum model of nephritis. In this model, T cell–specific silencing of STAT3 resulted in amelioration of nephrotoxic serum-induced kidney damage. Taken together, our results suggest that in mouse models of autoimmune nephritis, T cell–specific silencing of STAT3 can hamper their ability to help B cells to produce autoantibodies and induce cell tissue infiltration. We propose that STAT3 inhibition in T cells represents a novel approach in the treatment of SLE and lupus nephritis in particular.

scholarly journals Role of Hormonal Circuitry Upon T Cell Development in Chagas Disease: Possible Implications on T Cell Dysfunctions

2018 ◽  
Vol 9 ◽  
Author(s):  
Ana Rosa Pérez ◽  
Alexandre Morrot ◽  
Vinicius Frias Carvalho ◽  
Juliana de Meis ◽  
Wilson Savino
Keyword(s):  
T Cell ◽  
Chagas Disease ◽  
T Cell Development ◽  
Cell Development

The Role of Heme Oxygenase-1 in T Cell-Mediated Immunity: The All Encompassing Enzyme

2008 ◽  
Vol 14 (5) ◽  
pp. 454-464 ◽  
Author(s):  
Z. Xia ◽  
W. Zhong ◽  
J. Meyrowitz ◽  
Z. Zhang
Keyword(s):  
T Cell ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Cell Mediated Immunity

scholarly journals m6A demethylase ALKBH5 controls CD4+ T cell pathogenicity and promotes autoimmunity

2021 ◽  
Vol 7 (25) ◽  
pp. eabg0470
Author(s):  
Jing Zhou ◽  
Xingli Zhang ◽  
Jiajia Hu ◽  
Rihao Qu ◽  
Zhibin Yu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Messenger Rna ◽  
Interferon Γ ◽  
Autoimmune Encephalomyelitis ◽  
Cell Responses ◽  
Chemokine Ligand ◽  
The Central Nervous System ◽  
Chemokine Ligand 2

N6-methyladenosine (m6A) modification is dynamically regulated by “writer” and “eraser” enzymes. m6A “writers” have been shown to ensure the homeostasis of CD4+ T cells, but the “erasers” functioning in T cells is poorly understood. Here, we reported that m6A eraser AlkB homolog 5 (ALKBH5), but not FTO, maintains the ability of naïve CD4+ T cells to induce adoptive transfer colitis. In addition, T cell–specific ablation of ALKBH5 confers protection against experimental autoimmune encephalomyelitis. During the induced neuroinflammation, ALKBH5 deficiency increased m6A modification on interferon-γ and C-X-C motif chemokine ligand 2 messenger RNA (mRNA), thus decreasing their mRNA stability and protein expression in CD4+ T cells. These modifications resulted in attenuated CD4+ T cell responses and diminished recruitment of neutrophils into the central nervous system. Our findings reveal an unexpected specific role of ALKBH5 as an m6A eraser in controlling the pathogenicity of CD4+ T cells during autoimmunity.

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