Type I Interferons Suppress Anti-parasitic Immunity and Can Be Targeted to Improve Treatment of Visceral Leishmaniasis

Kumar, Rajiv; Bunn, Patrick T.; Singh, Siddharth; Ng, Susanna S.; de, Marcela Montes; Rivera, Fabian de Labastida; Chauhan, S. V. S.; Singh, Neetu; Faleiro, Rebecca J.; Edwards, Chelsea L.; Frame, Teija; Sheel, Meru; Austin, Rebecca; Lane, Steven; Bald, Tobias; Smyth, Mark J.; Hill, Geoffrey R.; Best, Shannon E.; Haque, Ashraful; Corvino, Dillon; Waddell, Nic; Koufariotis, Lambross; Mukhopadhay, Pamela; Rai, Madhukar; Chakravarty, Jaya; Singh, O. P.; Sacks, David L.; Nylén, Susanne; Uzonna, Jude; Engwerda, Christian

doi:10.1016/j.celrep.2020.01.099

Cited by 46 publications

(44 citation statements)

References 94 publications

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“…The role of IL-10 in negative regulation of Th1 responses has been highlighted by lethal outcomes of IL-10 knockout or neutralization in toxoplasma or trypanosome mouse infection models [ 37 ]. Many immunoregulatory molecules and pathways, most notably those associated with interleukin-10 (IL-10) production, are activated following infection, which can suppress antiparasitic CD4 + T cell functions [ 38 ]. Recent findings have suggested that IL-10 impairs the Th1 protective response and allows the parasites to survive in hydatid patients [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-374b-5p Regulates T Cell Differentiation and Is Associated with rEg.P29 Immunity

Zhu

et al. 2020

BioMed Research International

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Cystic echinococcosis (CE) is a zoonotic disease caused by Echinococcus granulosus (Eg) infection. Our previous study confirmed that recombinant Eg.P29 (rEg.P29) could protect against echinococcus granulosus secondary infection in sheep and mice. The aim of the study was to investigate the association between immunoprotection of rEg.P29 vaccine and mmu-miR-374b-5p (miR-374b-5p) and study the immunity influence of miR-374b-5p on CD4+ T cells in mice spleen. MiR-374b-5p level was significantly increased after the second-week and the fourth week of vaccination with rEg.P29. Overexpression of miR-374b-5p increased IFN-γ, IL-2, IL-17A mRNA levels and decreased IL-10 mRNA levels in CD4+ T cells. Moreover, the inhibition of miR-374b-5p decreased IFN-γ and IL-17A and increased IL-10 mRNA levels in CD4+ T cells; this was further confirmed by the flow cytometry. The vaccination of rEg.P29 enhanced miR-374b-5p expression that was associated with a higher Th1 and Th17 immune response, a lower IL-10 mRNA production with miR-374b-5p overexpression, a lower Th1 immune response, and a higher IL-10 mRNA levels with miR-374b-5p inhibitions. To sum up, these data suggest that miR-374b-5p may participate in rEg.P29 immunity by regulating Th1 and Th17 differentiation.

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Section: Discussionmentioning

confidence: 99%

MiR-374b-5p Regulates T Cell Differentiation and Is Associated with rEg.P29 Immunity

Zhu

et al. 2020

BioMed Research International

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“…Recently, whole lung transcriptomic analyses have confirmed that the induction of IFN‐I response genes occurs in a broad range of lung diseases including viral infection as well as in HDM‐dependent allergic airway inflammation 87 . Reports that IFN‐I can suppress IFNγ responses 88 and regulate the balance of T‐follicular versus T‐effector CD4 + T‐cell differentiation 89 may offer potential mechanisms for the enhancement of Th2 responses by IFN‐I.…”

Section: How Do Conventional Dcs Drive the Development Of Th2 Cells?mentioning

confidence: 98%

“…86 Recently, whole lung transcriptomic analyses have confirmed that the induction of IFN-I response genes occurs in a broad range of lung diseases including viral infection as well as in HDM-dependent allergic airway inflammation. 87 Reports that IFN-I can suppress IFNc responses 88 and regulate the balance of T-follicular versus T-effector CD4 + T-cell differentiation 89 may offer potential mechanisms for the enhancement of Th2 responses by IFN-I. IL-33 is an alarmin belonging to the IL-1 superfamily that binds a heterodimeric receptor comprising ST2 (IL1RL1) and IL-1 receptor accessory protein (IL1RAP) and activates NF-jB and MAP kinase pathways (Figure 1).…”

Section: The Need For Epithelial and Stromal Factors: Tslp Il-33 Ilmentioning

confidence: 99%

Dendritic cells in Th2 immune responses and allergic sensitization

et al. 2020

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Allergic responses are characterized by the activation of a specific subset of effector CD4 + T cells, the T-helper type 2 (Th2) cells, that respond to harmless environmental antigens causing inflammation and pathology. Th2 cells are also found in the context of parasite infections, where they can mediate parasite clearance and expulsion, and support tissue repair. The process that leads to the activation of Th2 cells in vivo is incompletely understood: while it has become clear that "conventional" dendritic cells are essential antigen-presenting cells for the initiation of Th2 immune responses, the molecules that are expressed by dendritic cells exposed to allergens, and the mediators that are produced as a consequence and signal to na€ ıve CD4 + T cells to promote their development into effector Th2, remain to be defined. Here we summarize recent developments in the identification of the dendritic cell subsets involved in Th2 responses, review potential mechanisms proposed to explain the generation of these immune responses, and discuss the direct and indirect signals that condition dendritic cells to drive the development of Th2 responses during allergen or parasite exposure.

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“…As an interferon-induced protein, IFI44 expression levels directly re ect IFN-α/β activity. IFN-α/β plays an important role in defending against infection from many parasites such as Leishmania donovani [28], Plasmodium [29], Toxoplasma [30], and Trypanosome brucei [31]. Therefore, it is speculated that IFI44 might have indirect anti-protozoan functions.…”

Section: Immune-related Proteinsmentioning

confidence: 99%

Protein Regulation Strategies of Mouse Spleen in Response to Babesia Microti Infection

Xue

Ren

Masoudi

et al. 2020

Preprint

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BackgroundBabesia is a protozoan parasite in red blood cells of some vertebrates. Some species of Babesia can cause zoonoses and cause great harm. As the largest immune organ in mammals, the spleen plays an important role in defending against Babesia infection. When infected with Babesia, the spleen is seriously injured, but it still actively initiates immunomodulatory responses.MethodsIn order to explore the molecular mechanisms underlying the immune regulation and self-repair of the spleen in response to infection, this study used data-independent acquisition (DIA) quantitative proteomics to analyse changes in expression levels of global proteins and changes in phosphorylation modification in spleen tissue after Babesia microti infection in mice.ResultsAfter the mice were infected with B. microti, their spleen were seriously damaged.Using bioinfor-matics methods to analyze the dynamic changes of a large number of proteins, we found that spleen still initiated immune response to deal with the infection, in which immune-related proteins played an important role, including CTSD, IFI44, ILF2, ILF, and STAT5A. In addition, some proteins related to iron metabolism were also involved in the repair of spleen against B. microti infection, including serotransferrin, lactoferrin, TfR1, and GCL. At the same time, the expression and phosphorylation of proteins related to the growth and development of the spleen also changed, including PKC-δ and MAPK3/1, Grb2, and PAK2. ConclusionsImmune-related proteins, iron metabolism-related proteins and growth and development-related proteins play an important important role in the regulation of spleen injury and maintenance of homeostasis. This study will provide important bases for the diagnosis and treatment of babesiosis.

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Type I Interferons Suppress Anti-parasitic Immunity and Can Be Targeted to Improve Treatment of Visceral Leishmaniasis

Cited by 46 publications

References 94 publications

MiR-374b-5p Regulates T Cell Differentiation and Is Associated with rEg.P29 Immunity

MiR-374b-5p Regulates T Cell Differentiation and Is Associated with rEg.P29 Immunity

Dendritic cells in Th2 immune responses and allergic sensitization

Protein Regulation Strategies of Mouse Spleen in Response to Babesia Microti Infection

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