The Role of MIF and IL-10 as Molecular Yin-Yang in the Modulation of the Host Immune Microenvironment During Infections: African Trypanosome Infections as a Paradigm

Stijlemans, Benoît; Schoovaerts, Maxime; Baetseĺier, Patrick De; Magez, Stefan; Trez, Carl De

doi:10.3389/fimmu.2022.865395

Cited by 3 publications

(1 citation statement)

References 256 publications

(332 reference statements)

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“…Several studies have repeatedly shown that IFN-γ is essential for parasite clearance and protective efficacy [ 53 , 55 ]. In malaria infection, IL-10 is a potent suppressor of several pro-inflammatory cytokines such as IFN-γ, making it detrimental to the cell-mediated immune response [ 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Elicitation of T-cell-derived IFN-γ-dependent immunity by highly conserved Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII)

Ren

Shi

et al. 2023

Parasites Vectors

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Background Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease has been underestimated. Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII) is an essential ligand for reticulocyte recognition and host cell invasion by P. ovale curtisi. However, the genomic variation, antigenicity and immunogenicity of PocDBP-RII remain major knowledge gaps. Methods A total of 93 P. ovale curtisi samples were collected from migrant workers who returned to China from 17 countries in Africa between 2012 and 2016. The genetic polymorphism, natural selection and copy number variation (CNV) were investigated by sequencing and real-time PCR. The antigenicity and immunogenicity of the recombinant PocDBP-RII (rPocDBP-RII) protein were further examined, and the humoral and cellular responses of immunized mice were assessed using protein microarrays and flow cytometry. Results Efficiently expressed and purified rPocDBP-RII (39 kDa) was successfully used as an antigen for immunization in mice. The haplotype diversity (Hd) of PocDBP-RII gene was 0.105, and the nucleotide diversity index (π) was 0.00011. No increased copy number was found among the collected isolates of P. ovale curtisi. Furthermore, rPocDBP-RII induced persistent antigen-specific antibody production with a serum IgG antibody titer of 1: 16,000. IFN-γ-producing T cells, rather than IL-10-producing cells, were activated in response to the stimulation of rPocDBP-RII. Compared to PBS-immunized mice (negative control), there was a higher percentage of CD4+CD44highCD62L− T cells (effector memory T cells) and CD8+CD44highCD62L+ T cells (central memory T cells) in rPocDBP-RII‑immunized mice. Conclusions PocDBP-RII sequences were highly conserved in clinical isolates of P. ovale curtisi. rPocDBP-RII protein could mediate protective blood-stage immunity through IFN-γ-producing CD4+ and CD8+ T cells and memory T cells, in addition to inducing specific antibodies. Our results suggested that rPocDBP-RII protein has potential as a vaccine candidate to provide assessment and guidance for malaria control and elimination activities. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Elicitation of T-cell-derived IFN-γ-dependent immunity by highly conserved Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII)

Ren

Shi

et al. 2023

Parasites Vectors

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Bioengineered stem cell membrane functionalized nanoparticles combine anti-inflammatory and antimicrobial properties for sepsis treatment

Quan

et al. 2023

J Nanobiotechnol

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Background Sepsis is a syndrome of physiological, pathological and biochemical abnormalities caused by infection. Although the mortality rate is lower than before, many survivors have persistent infection, which means sepsis calls for new treatment. After infection, inflammatory mediators were largely released into the blood, leading to multiple organ dysfunction. Therefore, anti-infection and anti-inflammation are critical issues in sepsis management. Results Here, we successfully constructed a novel nanometer drug loading system for sepsis management, FZ/MER-AgMOF@Bm. The nanoparticles were modified with LPS-treated bone marrow mesenchymal stem cell (BMSC) membrane, and silver metal organic framework (AgMOF) was used as the nanocore for loading FPS-ZM1 and meropenem which was delivery to the infectious microenvironments (IMEs) to exert dual anti-inflammatory and antibacterial effects. FZ/MER-AgMOF@Bm effectively alleviated excessive inflammatory response and eliminated bacteria. FZ/MER-AgMOF@Bm also played an anti-inflammatory role by promoting the polarization of macrophages to M2. When sepsis induced by cecal ligation and puncture (CLP) challenged mice was treated, FZ/MER-AgMOF@Bm could not only reduce the levels of pro-inflammatory factors and lung injury, but also help to improve hypothermia caused by septic shock and prolong survival time. Conclusions Together, the nanoparticles played a role in combined anti-inflammatory and antimicrobial properties, alleviating cytokine storm and protecting vital organ functions, could be a potential new strategy for sepsis management.

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From helping to regulating – A transcriptomic profile of Ifng+ Il10+ Il21+ Cd4+ Th1 cells indicates their role in regulating inflammation during experimental trypanosomosis

Nguyen

Magez²,

Radwanska³

2023

Front. Trop. Dis

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IntroductionTrypanosoma evansi parasite infections cause a chronic animal wasting disease called Surra, and cases of atypical Human Trypanosomosis (aHT). In experimental models, T. evansi infections are hallmarked by the early onset of excessive inflammation. Therefore, balancing the production of inflammatory cytokines by anti-inflammatory IL-10 is crucial for prolonged survival.MethodsTo improve the understanding of trypanosomosis induced immunopathology, we used scRNA-seq data from an experimental chronic T. evansi infection mouse model, resembling natural infection in terms of disease characteristics. Results and discussionFor the first time, obtained results allowed to assess the transcriptomic profile and heterogeneity of splenic CD4+ T cell subsets, during a trypanosome infection. Here, the predominant subpopulation of T cells was represented by Tbx21(T-bet)+Ccr5+ Id2+ type 1 helper T cells (Th1), followed by Icos+ Cxcr5+Follicular T helper cells (Tfh) and very minor fraction of Il2ra(CD25)+Foxp3+ regulatory T cells (Tregs). Interestingly, the profile of Th1 cells shows that besides Ifng, these cells express high levels of Il10 and Il21, coding for anti-inflammatory and immunoregulatory cytokines. This coincides with the elevated expression of key genes involved in IL-10 and IL-21 secretion pathway such as Stat1 and Stat3, as well as the transcriptional factors Prdm1 (Blimp 1), and Maf (c-Maf). In contrast, there is virtually no IL-10 transcription detected in the Treg population. Finally, differential gene expression and gene ontology analysis of infection-induced Ifng+ Il10+ Il21+ Th1 cells highlights their suppressive function on T cell activation, differentiation and INF-γ production itself. This indicates that during trypanosome infections, the Ifng+ Il10+ Il21+ Th1 cells, rather than Tregs, assume an immune regulatory role that is needed for dampening inflammation.

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The Role of MIF and IL-10 as Molecular Yin-Yang in the Modulation of the Host Immune Microenvironment During Infections: African Trypanosome Infections as a Paradigm

Cited by 3 publications

References 256 publications

Elicitation of T-cell-derived IFN-γ-dependent immunity by highly conserved Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII)

Elicitation of T-cell-derived IFN-γ-dependent immunity by highly conserved Plasmodium ovale curtisi Duffy binding protein domain region II (PocDBP-RII)

Bioengineered stem cell membrane functionalized nanoparticles combine anti-inflammatory and antimicrobial properties for sepsis treatment

From helping to regulating – A transcriptomic profile of Ifng+ Il10+ Il21+ Cd4+ Th1 cells indicates their role in regulating inflammation during experimental trypanosomosis

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