Regulatory T cells in acute and chronic human Chikungunya infection

Gois, Bruna Macêdo; Peixoto, Rephany Fonseca; Guerra-Gomes, Isabel Cristina; Palmeira, Pedro Henrique de Sousa; Dias, Cínthia Nóbrega de Sousa; Araújo, Josélio Maria Galvão de; Veras, Robson Cavalcante; Medeiros, Isac Araújo; Azevedo, Fátima de Lourdes Assunção Araújo de; Boyton, Rosemary J.; Altmann, Daniel M.; Keesen, Tatjana Souza Lima

doi:10.1016/j.micinf.2021.104927

Cited by 9 publications

(8 citation statements)

References 24 publications

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“…For the main cell types in Figure 3B , Pearson correlations were determined for the NES scores for Adults vs. Mice Ft 7 dpi and Children vs. Mice Ft 7 dpi ( Figure 3C ). Correlations were highly significant for the main cell types involved in CHIKV arthritis; T cells ( 56 – 58 ), monocyte/macrophages ( 45 , 51 , 55 ) and NK cells ( 59 ), and to a lesser extent neutrophils ( 54 , 60 ), regulatory T cells ( 61 , 62 ) and dendritic cells ( 13 ) ( Figure 3C ). Coefficients of determination (r 2 ) were generally not so high ( Figure 3C ), likely reflecting the influence of the aforementioned lymphopenia.…”

Section: Resultsmentioning

confidence: 98%

Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model

et al. 2022

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IntroductionAn adult wild-type C57BL/6J mouse model of chikungunya virus (CHIKV) infection and disease has been extensively used to study the alphaviral arthritic immunopathology and to evaluate new interventions. How well mouse models recapitulate the gene expression profiles seen in humans remains controversial.MethodsHerein we perform a comparative transcriptomics analysis using RNA-Seq datasets from the C57BL/6J CHIKV mouse model with datasets obtained from adults and children acutely infected with CHIKV.ResultsDespite sampling quite different tissues, peripheral blood from humans and feet from mice, gene expression profiles were quite similar, with an overlap of up to ≈50% for up-regulated single copy orthologue differentially expressed genes. Furthermore, high levels of significant concordance between mouse and human were seen for immune pathways and signatures, which were dominated by interferons, T cells and monocyte/macrophages. Importantly, predicted responses to a series of anti-inflammatory drug and biologic treatments also showed cogent similarities between species.DiscussionComparative transcriptomics and subsequent pathway analysis provides a detailed picture of how a given model recapitulates human gene expression. Using this method, we show that the C57BL/6J CHIKV mouse model provides a reliable and representative system in which to study CHIKV immunopathology and evaluate new treatments.

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Section: Resultsmentioning

confidence: 98%

Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model

et al. 2022

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“…Several studies investigated the function of regulatory T cells (Treg) in the CHIKV disease pathogenesis [ 107 , 108 ]. The frequency of Treg was lower in acute and chronic CHIKV compared to recovered cases.…”

Section: The Host Adaptive Immune Responses Against Chikv Infectionmentioning

confidence: 99%

“…In line, the IL-10 level was higher in recovered than in acute and chronic cases [ 107 ]. In addition, impaired functions of Treg were reported, which were characterized by lower expression PD-1, CTLA-4, and TGF-β [ 108 ]. This finding suggests that during acute and chronic CHIKV disease, Treg frequency and function are impaired and that normalization of Treg is associated with disease resolution.…”

Section: The Host Adaptive Immune Responses Against Chikv Infectionmentioning

confidence: 99%

Understanding the Biology and Immune Pathogenesis of Chikungunya Virus Infection for Diagnostic and Vaccine Development

Hakim¹,

Aman²

2022

Viruses

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Chikungunya virus, the causative agent of chikungunya fever, is generally characterized by the sudden onset of symptoms, including fever, rash, myalgia, and headache. In some patients, acute chikungunya virus infection progresses to severe and chronic arthralgia that persists for years. Chikungunya infection is more commonly identified in tropical and subtropical regions. However, recent expansions and epidemics in the temperate regions have raised concerns about the future public health impact of chikungunya diseases. Several underlying factors have likely contributed to the recent re-emergence of chikungunya infection, including urbanization, human travel, viral adaptation to mosquito vectors, lack of effective control measures, and the spread of mosquito vectors to new regions. However, the true burden of chikungunya disease is most likely to be underestimated, particularly in developing countries, due to the lack of standard diagnostic assays and clinical manifestations overlapping with those of other endemic viral infections in the regions. Additionally, there have been no chikungunya vaccines available to prevent the infection. Thus, it is important to update our understanding of the immunopathogenesis of chikungunya infection, its clinical manifestations, the diagnosis, and the development of chikungunya vaccines.

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“…Treg cell accumulation has been observed in peripheral blood, secondary lymphoid organs and target tissues of chronic bacterial, viral and parasitic infections in both mice and humans (6, 8). Moreover, decreased numbers of Treg cells have been reported during the acute phase of a few infections, such as those caused by Toxoplasma gondii (9, 10), Listeria monocitogenes (9), vaccinia virus (9), LMCV clone Armstrong (11), and more recently, Chikungunya virus (12). These findings underscore the complexity of Treg cell dynamics and illustrate the context-dependent roles in different infectious scenarios.…”

Section: Introductionmentioning

confidence: 99%

CD39 expression by regulatory T cells drives CD8+ T cell suppression during experimentalTrypanosoma cruziinfection

Araujo Furlan,

Boccardo,

Rodriguez

et al. 2023

Preprint

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An imbalance between suppressor and effector immune responses may preclude cure in chronic parasitic diseases. In the case of Trypanosoma cruzi infection, specialized regulatory Foxp3+ T (Treg) cells suppress protective type-1 effector responses. Herein, we investigated the kinetics and underlying mechanisms behind the regulation of protective parasite-specific CD8+ T cell immunity during acute T. cruzi infection. Using the DEREG mouse model, we found that Treg cells play a critical role during the initial stages after T. cruzi infection, subsequently influencing CD8+ T cells. Early Treg cell depletion increased the frequencies of polyfunctional short-lived, effector T cell subsets, without affecting memory precursor cell formation or the expression of activation markers. In addition, Treg cell depletion during early infection minimally affected the antigen-presenting cell response but it boosted CD4+ T cell responses before the development of anti-parasite effector CD8+ T cell responses. Crucially, the absence of CD39 expression on Treg cells significantly bolstered effector parasite-specific CD8+ T cell responses, leading to improved parasite control during T. cruzi infection. Our work underscores the crucial role of Treg cells in regulating protective anti-parasite immunity and provides evidence that CD39 expression by Treg cells represents a key immunomodulatory mechanism in this infection model.

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Regulatory T cells in acute and chronic human Chikungunya infection

Cited by 9 publications

References 24 publications

Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model

Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model

Understanding the Biology and Immune Pathogenesis of Chikungunya Virus Infection for Diagnostic and Vaccine Development

CD39 expression by regulatory T cells drives CD8+ T cell suppression during experimentalTrypanosoma cruziinfection

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