Expression of negative immune regulatory molecules, pro-inflammatory chemokine and cytokines in immunopathology of ECM developing mice

Khandare, Ashwin V.; Bobade, Deepali; Deval, Mangesh; Patil, Tushar; Saha, Bhaskar; Prakash, D.

doi:10.1016/j.actatropica.2017.04.025

Cited by 16 publications

(13 citation statements)

References 23 publications

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“…The copyright holder for this preprint (which this version posted April 20, 2021. ; https://doi.org/10.1101/2021.04.19.440453 doi: bioRxiv preprint Acute malaria is associated with strong induction of co-inhibitory molecules on T cells. This was demonstrated in humans (Abel et al, 2018;Illingworth et al, 2013) as well as in animal models (Khandare et al, 2017;Lepenies et al, 2007). In chronic antigen exposure settings, expression of these molecules is associated with T cell exhaustion, especially of CD8 + T cells (Cornberg et al, 2013;Ochel et al, 2016).…”

Section: Discussionmentioning

confidence: 88%

T cells expressing multiple co-inhibitory molecules in acute malaria are not exhausted but exert a suppressive function

Brandi

Lehmann

Kaminski

et al. 2021

Preprint

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Overwhelming activation of T cells in acute malaria is associated with severe outcomes. Thus, counter-regulation by anti-inflammatory mechanisms is indispensable for an optimal resolution of disease. Using Plasmodium berghei ANKA (PbA) infection of C57BL/6 mice, we performed a comprehensive analysis of co-inhibitory molecules expressed on CD4+ and CD8+ T cells using an unbiased cluster analysis approach. We identified similar T cell clusters co-expressing several co-inhibitory molecules like programmed cell death protein 1 (PD-1) and lymphocyte activation gene 3 (LAG-3) in the CD4+ and the CD8+ T cell compartment. Interestingly, despite expressing co-inhibitory molecules, which are associated with T cell exhaustion in chronic settings, these T cells were more functional compared to activated T cells that were negative for co-inhibitory molecules. However, T cells expressing high levels of PD-1 and LAG-3 also conferred suppressive capacity and thus resembled type I regulatory T cells. To our knowledge, this is the first description of malaria-induced CD8+ T cells with suppressive capacity. In conclusion, we demonstrate that malaria-induced T cells expressing co-inhibitory molecules are not exhausted but acquire additional suppressive capacity, which might represent an immune regulatory pathway to prevent further activation of T cells during acute malaria.

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Section: Discussionmentioning

confidence: 88%

T cells expressing multiple co-inhibitory molecules in acute malaria are not exhausted but exert a suppressive function

Brandi

Lehmann

Kaminski

et al. 2021

Preprint

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“…It is thought that certain infectious diseases may induce cognitive and behavioural deficits 34 – 36 . Malaria is a systemic disorder that can affect the central nervous system and the diseases caused by Plasmodium species capable of affecting the brain can affect the cerebellum, hippocampus, olfactory bulb and the cerebral cortex, both in humans 37 – 39 and experimental models 40 – 43 . The hippocampus is involved in memory consolidation and anxiety.…”

Section: Discussionmentioning

confidence: 99%

Immune system challenge improves recognition memory and reverses malaria-induced cognitive impairment in mice

Sousa

Ribeiro-Gomes

Almeida

et al. 2021

Sci Rep

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The immune system plays a role in the maintenance of healthy neurocognitive function. Different patterns of immune response triggered by distinct stimuli may affect nervous functions through regulatory or deregulatory signals, depending on the properties of the exogenous immunogens. Here, we investigate the effect of immune stimulation on cognitive-behavioural parameters in healthy mice and its impact on cognitive sequelae resulting from non-severe experimental malaria. We show that immune modulation induced by a specific combination of immune stimuli that induce a type 2 immune response can enhance long-term recognition memory in healthy adult mice subjected to novel object recognition task (NORT) and reverse a lack of recognition ability in NORT and anxiety-like behaviour in a light/dark task that result from a single episode of mild Plasmodium berghei ANKA malaria. Our findings suggest a potential use of immunogens for boosting and recovering recognition memory that may be impaired by chronic and infectious diseases and by the effects of ageing.

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“…Accumulated evidences indicated that an imbalance in pro- and anti-inflammatory immune responses to Plasmodium infection, disruption of blood-brain barrier (BBB) and endothelial cell activation are central pathophysiological processes in the development of CM [5]. The pathogenesis of CM likely involves excess production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), gamma interferon (IFN-γ), interleukin-1 (IL-1), and IL-12 [6–8]. The up-regulated expression of pro-inflammatory cytokines induces adhesion molecules such as ICAM-1, VCAM-1 and CD36 in brain endothelial cells.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Plasmodium berghei Homologues of T-cell Immunomodulatory Protein as a New Potential Candidate for Protecting against Experimental Cerebral Malaria

Zhou

et al. 2019

Korean J Parasitol

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The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.

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Expression of negative immune regulatory molecules, pro-inflammatory chemokine and cytokines in immunopathology of ECM developing mice

Cited by 16 publications

References 23 publications

T cells expressing multiple co-inhibitory molecules in acute malaria are not exhausted but exert a suppressive function

T cells expressing multiple co-inhibitory molecules in acute malaria are not exhausted but exert a suppressive function

Immune system challenge improves recognition memory and reverses malaria-induced cognitive impairment in mice

Characterization of Plasmodium berghei Homologues of T-cell Immunomodulatory Protein as a New Potential Candidate for Protecting against Experimental Cerebral Malaria

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