Interleukin-17 Contributes to Chikungunya Virus-Induced Disease

Liu, Xiang; Poo, Yee-Suan; Alves, Juliana Cardoso; Almeida, Roque Pacheco de; Mostafavi, Helen; Tang, Patrick Chun Hean; Bucala, Richard; Teixeira, Mauro Martins; Taylor, Adam; Zaid, Ali; Mahalingam, Suresh

doi:10.1128/mbio.00289-22

Cited by 13 publications

(15 citation statements)

References 26 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of the top cytokines and transcriptional regulators ( Figure 4 ) are well described in the CHIKV literature, and as expected are dominated by interferon (IFN) and Th1 responses ( 1 , 15 , 40 , 41 , 54 , 60 , 63 – 66 ). Perhaps surprising is the absence of CCL2/CCR2 as an USR, even though CCL2 is a highly significant DEG, and is well described for CHIKV infections ( 45 , 55 , 67 ).…”

Section: Resultssupporting

confidence: 63%

“…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%

See 1 more Smart Citation

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

et al. 2022

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 63%

Section: Resultsmentioning

confidence: 98%

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

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Infected macrophages serve as a possible reservoir for CHIKV and may contribute to the persistent inflammation driven by secretion of cytokines (e.g., IL-6, CCL2) and joint pain associated with infection [ 1 , 41 ]. Furthermore, during the inflammatory response, cytokines mediate the recruitment of neutrophils and monocytes/macrophages that are also involved in the production of direct-acting hyperalgesic mediators, such as PGE 2 , leading to mechanical hypernociception and chronic CHIKV in patients [ 3 , 10 , 47 , 48 ]. In our study, CHIKV-infected animals showed prolonged hypernociception, even after the inflammation was resolved, indicating that there may be other mechanisms involved in pain persistence.…”

Section: Discussionmentioning

confidence: 99%

Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection

Araújo

Costa

Santos

et al. 2022

Cells

Self Cite

View full text Add to dashboard Cite

Chikungunya (CHIKV) is an arthritogenic alphavirus that causes a self-limiting disease usually accompanied by joint pain and/or polyarthralgia with disabling characteristics. Immune responses developed during the acute phase of CHIKV infection determine the rate of disease progression and resolution. Annexin A1 (AnxA1) is involved in both initiating inflammation and preventing over-response, being essential for a balanced end of inflammation. In this study, we investigated the role of the AnxA1-FPR2/ALX pathway during CHIKV infection. Genetic deletion of AnxA1 or its receptor enhanced inflammatory responses driven by CHIKV. These knockout mice showed increased neutrophil accumulation and augmented tissue damage at the site of infection compared with control mice. Conversely, treatment of wild-type animals with the AnxA1 mimetic peptide (Ac2–26) reduced neutrophil accumulation, decreased local concentration of inflammatory mediators and diminished mechanical hypernociception and paw edema induced by CHIKV-infection. Alterations in viral load were mild both in genetic deletion or with treatment. Combined, our data suggest that the AnxA1-FPR2/ALX pathway is a potential therapeutic strategy to control CHIKV-induced acute inflammation and polyarthralgia.

show abstract

“…In a recent study, IL-17A has been reported to be associated with tissue inf lammation as well as neutrophil infiltration in CHIKV-induced RA [28]. In another recent study on IL-17 in RRV disease, IL-17 has been found to be responsible for RRV-induced arthritis and myositis [52].…”

Section: Alphavirus Disease and Host Immune Responsementioning

confidence: 96%

“…Arthritogenic alphaviruses such as CHIKV, Mayaro virus (MAYV), RRV and O'nyong-nyong virus are associated with rheumatic disease and are the primary cause of infectious arthropathies worldwide [28]. Generally, acute fever, skin rash, malaise, fatigue, myalgia and arthralgia are the common clinical signs shared by most arthrogenic alphavirus infections.…”

Section: Alphavirus Disease and Host Immune Responsementioning

confidence: 99%

Host Immune Responses to Arthritogenic Alphavirus Infection, with Emphasis on Type I IFN Responses

Tang

Liu

2022

Zoonoses

Self Cite

View full text Add to dashboard Cite

Arthritogenic alphaviruses, such as Ross River virus, chikungunya virus and O’nyong-nyong virus, cause endemic disease globally and are a major public health concern. The hallmarks of arthritogenic alphavirus disease are debilitating pain, and potentially chronic inflammation of the muscles, thus influencing quality of life. The type I IFN response is a major component of the innate immune response against arthritogenic alphaviruses, and is essential in inhibiting viral replication and dissemination. Type I IFNs are induced during early stages of infection and are essential for the activation of the antiviral innate immune response. They also link the innate immune response and the activation of adaptive immunity. This review focuses on the host immune response, particularly that involving type I IFN, in arthritogenic alphavirus disease.

show abstract

Interleukin-17 Contributes to Chikungunya Virus-Induced Disease

Abstract: CHIKV has been prevalent in Africa, Asia, and the Indian Ocean Islands for decades. There are currently no clinically approved vaccines or specific antiviral drugs targeting CHIKV.

Cited by 13 publications

References 26 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

Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection

Host Immune Responses to Arthritogenic Alphavirus Infection, with Emphasis on Type I IFN Responses

Contact Info

Product

Resources

About