Angiotensin II Is a New Component Involved in Splenic T Lymphocyte Responses during Plasmodium berghei ANKA Infection

Silva-Filho, João Luiz; Souza, Mariana C.; Ferreira-DaSilva, Claudio Teixeira; Silva, Leandro Souza; Costa, Maria Fernanda Souza; Pádua, Tatiana Almeida; Henriques, Maria das Graças; Morrot, Alexandre; Savino, Wilson; Caruso-Neves, Celso; Pinheiro, Ana Acácia S.

doi:10.1371/journal.pone.0062999

Cited by 29 publications

(69 citation statements)

References 61 publications

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“…Our group and others have focused on describing the role of RAS effector molecules, especially angiotensin II (Ang II) and its receptor AT 1 (AT 1 R), in the regulation of adaptive immune response56789101112131415161718192021. Ang II has been proposed to have pro-inflammatory effects, via AT 1 R8910111213151617181920, however the cellular mechanisms underlying the role of AT 1 R in the regulation of antigen-specific T cells in different pathologies are not clear yet.…”

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confidence: 99%

“…It has been demonstrated that T cells possess a functional RAS and are capable of producing Ang II10111213142021. In these cells, Ang II promotes proliferation, differentiation, effector function, adhesion, migration, and acts as a co-stimulatory molecule important to T-cell activation, and all these effects are mediated by AT 1 R binding56791011121314152021.…”

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confidence: 99%

“…In these cells, Ang II promotes proliferation, differentiation, effector function, adhesion, migration, and acts as a co-stimulatory molecule important to T-cell activation, and all these effects are mediated by AT 1 R binding56791011121314152021. Importantly, AT 1 R expression is upregulated in T cells during activation in vitro and in vivo , for instance during the blood stage of Plasmodium berghei ANKA (PbA) infection, strengthening the importance of this receptor for T-cell response11121315. In this regard, AT 1 R is involved in the higher production of pro-inflammatory cytokines by CD4 + T cells and perforin by CD8 + T cells, and increased capacity to adhere and migrate through upregulation of adhesion molecules and chemokine receptors1213.…”

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confidence: 99%

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Angiotensin II type-1 receptor (AT1R) regulates expansion, differentiation, and functional capacity of antigen-specific CD8+ T cells

Silva-Filho

Caruso-Neves

Pinheiro

2016

Sci Rep

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Angiotensin II (Ang II) and its receptor AT1 (AT1R), an important effector axis of renin-angiotensin system (RAS), have been demonstrated to regulate T-cell responses. However, these studies characterized Ang II and AT1R effects using pharmacological tools, which do not target only Ang II/AT1R axis. The specific role of AT1R expressed by antigen-specific CD8+ T cells is unknown. Then we immunized transgenic mice expressing a T-cell receptor specific for SIINFEKL epitope (OT-I mice) with sporozoites of the rodent malaria parasite Plasmodium berghei expressing the cytotoxic epitope SIINFEKL. Early priming events after immunization were not affected but the expansion and contraction of AT1R-deficient (AT1R−/−) OT-I cells was decreased. Moreover, they seemed more activated, express higher levels of CTLA-4, PD-1, LAG-3, and have decreased functional capacity during the effector phase. Memory AT1R−/− OT-I cells exhibited higher IL-7Rα expression, activation, and exhaustion phenotypes but less cytotoxic capacity. Importantly, AT1R−/− OT-I cells show better control of blood parasitemia burden and ameliorate mice survival during lethal disease induced by blood-stage malaria. Our study reveals that AT1R in antigen-specific CD8+ T cells regulates expansion, differentiation, and function during effector and memory phases of the response against Plasmodium, which could apply to different infectious agents.

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Angiotensin II type-1 receptor (AT1R) regulates expansion, differentiation, and functional capacity of antigen-specific CD8+ T cells

Silva-Filho

Caruso-Neves

Pinheiro

2016

Sci Rep

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“…The latter finding may be related to the anti-plasmodial activity of AT-II (Torres et al 2015). Interestingly, inhibition of either ACE or the AT 1 -receptor with captopril or losartan protects against murine CM by decreasing splenic T-cell activation (Silva-Filho et al 2013).…”

Section: Altered Vasomotor Activitymentioning

confidence: 96%

The immunological balance between host and parasite in malaria

Deroost

Pham

Opdenakker

et al. 2015

FEMS Microbiology Reviews

104

117

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One sentence summary: The intricate balance between anti-malarial immunity and parasite virulence factors including immune evasion mechanisms determine the outcome of malaria infections, as imbalances resulting in exaggerated parasite growth, excessive inflammation or the combination of both result in severe pathology. Editor: Christian van Ooij ABSTRACTCoevolution of humans and malaria parasites has generated an intricate balance between the immune system of the host and virulence factors of the parasite, equilibrating maximal parasite transmission with limited host damage. Focusing on the blood stage of the disease, we discuss how the balance between anti-parasite immunity versus immunomodulatory and evasion mechanisms of the parasite may result in parasite clearance or chronic infection without major symptoms, whereas imbalances characterized by excessive parasite growth, exaggerated immune reactions or a combination of both cause severe pathology and death, which is detrimental for both parasite and host. A thorough understanding of the immunological balance of malaria and its relation to other physiological balances in the body is of crucial importance for developing effective interventions to reduce malaria-related morbidity and to diminish fatal outcomes due to severe complications. Therefore, we discuss in this review the detailed mechanisms of anti-malarial immunity, parasite virulence factors including immune evasion mechanisms and pathogenesis. Furthermore, we propose a comprehensive classification of malaria complications according to the different types of imbalances.

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“…Ang-II modulates T cell responses in experimental autoimmune encephalitis, wherein CD4 + T cells produce elevated Ang-II levels and increase secretion of IL-17 and IFNγ that is reversed by ARBs or ACE-inhibitors (43). Ang-II also promotes IL-17 production from splenic T cells following malaria infection in mice, which is largely attenuated by losartan (44). Together, these data suggest that the proinflammatory actions of RAS are likely mediated through T cell responses and enhanced IL-17 production.…”

Section: Il-17 and Associated Mediatorsmentioning

confidence: 99%

Central role of IL-17/Th17 immune responses and the gut microbiota in the pathogenesis of intestinal fibrosis

Ray

Salvo

Pizarro

2014

Current Opinion in Gastroenterology

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Purpose of review Intestinal fibrosis is a serious, yet common, outcome in patients with inflammatory bowel disease (IBD). Despite advances in developing novel treatment modalities to control chronic gut inflammation characteristic of IBD, no effective anti-fibrotic therapies exist to date. As such, a deeper understanding of the molecular mechanisms underlying intestinal fibrosis and the availability of relevant animal models are critical to move this area of investigation forward. Recent findings Emerging concepts in the pathogenesis of intestinal fibrosis include the central role of interleukin (IL)-17 and Th17 immune responses, although their precise contribution to chronic inflammation and IBD remains controversial. Other novel mediators of intestinal fibrosis, such as tumor necrosis factor (TNF)-like ligand 1A (TL1A) and components of the renin-angiotensin system, support the importance of IL-17. Additionally, recent studies utilizing novel mouse models highlight the significance of the gut microbiota and link components of bacterial sensing, including nucleotide-binding oligomerization domain-containing protein 2 (NOD2), to IL-17/Th17 immune responses in the development of inflammation-associated intestinal fibrosis. Summary Recent progress in identifying key mediators, novel animal models, and important mechanistic pathways in the pathogenesis of intestinal fibrosis hold promise for the development of effective anti-fibrotics in an area of significant, unmet clinical need.

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Angiotensin II Is a New Component Involved in Splenic T Lymphocyte Responses during Plasmodium berghei ANKA Infection

Cited by 29 publications

References 61 publications

Angiotensin II type-1 receptor (AT1R) regulates expansion, differentiation, and functional capacity of antigen-specific CD8+ T cells

Angiotensin II type-1 receptor (AT1R) regulates expansion, differentiation, and functional capacity of antigen-specific CD8+ T cells

The immunological balance between host and parasite in malaria

Central role of IL-17/Th17 immune responses and the gut microbiota in the pathogenesis of intestinal fibrosis

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