IFN-β differentially regulates the function of T cell subsets in MS and EAE

Kavrochorianou, Nadia; Markogiannaki, Melina; Haralambous, Sylva

doi:10.1016/j.cytogfr.2016.03.013

Cited by 18 publications

(12 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is reported that IFN-β has been used for the control of multiple sclerosis, possibly via inhibitory effect on the function T helper 1 (Th1) cells, although the detail mode of action still not fully elucidated [45,46]. In the case of TB, the inhibition of type I IFN signaling in DCs mediated by STAT1 results into high expression of IL-12 and also stimulate the differentiation of T cells into Th1 cell population [44].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Type I Interferon Signaling abrogates Early Mycobacterium bovis Infection

Zhou

Hussain

Zhang

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Mycobacterium bovis (M. bovis) is the central causative agent of bovine tuberculosis; however, it also caused serious infection in human beings. Type I IFNs is a key factor in reducing viral multiplication and modulate host immune defense against viral infection. However, the regulatory pathways of type I IFN signaling during Mycobactrium bovis (M. bovis) infection are not yet fully explored. Here, we investigate the role of type I IFN signaling on the pathogenesis of M. bovis infection in mice. Methods: C57BL/6 mice were treated with IFNAR1-blocking antibody or Isotype control 24 hour before M. bovis infection. After 21 and 84 days of infection mice were sacrificed, for analysis of type I IFN signaling on the pathogenesis of M. bovis. qRT-PCR and ELISA was performed to detect the expression of type I IFNs and relative gene. M. bovis induced lung lesions and viable bacterial count was assessed by conducting histopathology and CFU assay. Results: We observed an abundant expression of type I IFNs in the blood serum and lung tissues of M. bovis infected mice. In vivo blockade of type I IFN signaling reduced the recruitment of neutrophils to the lung tissue, mediate the activation of macrophages toward a pro-inflammatory profile and regulate the inflammatory cytokine production; however, no impact on T cell recruitment and activation in the early acute phase of infection was observed. Additionally, blocking of type I IFN signaling reduces bacterial burden in infected mice than untreated infected mice. Conclusions: Altogether, our results reveal that type I IFN mediates a balance between infection-mediated inflammatory reactions and pathogen’s control mechanism of the host during M. bovis infection. Thus, modulating type I IFN signaling could be exploited as therapeutic strategies against a large repertoire of inflammatory disorders, including tuberculosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of Type I Interferon Signaling abrogates Early Mycobacterium bovis Infection

Zhou

Hussain

Zhang

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Previously, IFN-β has been used for the control of multiple sclerosis, possibly via inhibitory effect on the function of T helper 1 (Th1) cells, but the detailed mode of action is not fully elucidated yet [43,44]. In the case of TB, inhibition of Type I IFN signaling in DCs mediated by STAT1 results into high expression of IL-12 and also stimulate the differentiation of T cells into Th1 cell population [42].…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that B cell-restricted Myd88 deficient mouse showed an increased M2 macrophages in the lungs tissue during M. tuberculosis infection, which is associated with increased bacterial load and reduced the severity of pathology [43]. Furthermore, C-type lectin receptor (DCIR) deficiency resulted inhibition of type I IFN signaling, which in turn leads macrophage activation into an antimicrobial M1 phenotype [44]. In line with these results, blockade of type I IFN signaling modulate macrophage polarization toward to a proinflammatory profile.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of Type I Interferon Signaling Abrogates Early Mycobacterium bovis Infection

Zhou

Hussain

Zhang

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Mycobacterium bovis (M. bovis) is the principal causative agent of bovine tuberculosis; however, it may also cause serious infection in human being. Type I IFN is a key factor in reducing viral multiplication and modulating host immune response against viral infection. However, the regulatory pathways of Type I IFN signaling during M. bovis infection are not yet fully explored. Here, we investigate the role of Type I IFN signaling in the pathogenesis of M. bovis infection in mice. Methods: C57BL/6 mice were treated with IFNAR1-blocking antibody or Isotype control 24 hour before M. bovis infection. After 21 and 84 days of infection, mice were sacrificed and role of Type I IFN signaling in the pathogenesis of M. bovis was investigated. ELISA and qRT-PCR was performed to detect the expression of Type I IFNs and related genes. M. bovis induced lung lesions were assessed by histopathological examination and viable bacterial count was determined by CFU assay. Results: We observed an abundant expression of Type I IFNs in the serum and lung tissues of M. bovis infected mice. In vivo blockade of Type I IFN signaling reduced the recruitment of neutrophils to the lung tissue, mediated the activation of macrophages leading to an increased pro-inflammatory profile and regulated the inflammatory cytokine production. However, no impact was observed on T cell recruitment and activation in the early acute phase of infection. Additionally, blocking of type I IFN signaling reduced bacterial burden in the infected mice as compared to untreated infected mice. Conclusions: Altogether, our results reveal that Type I IFN mediates a balance between M. bovis-mediated inflammatory reaction and host defense mechanism. Thus, modulating Type I IFN signaling could be exploited as a therapeutic strategy against a large repertoire of inflammatory disorders including tuberculosis.

show abstract

“…The mechanisms of action of type I IFNs in MS are complex and involve effects at multiple levels. Type I IFNs may reduce the trafficking of inflammatory cells across the blood-brain barrier, induce apoptosis of autoreactive T cells, increase the levels of anti-inflammatory cytokines (IL-10, IL-4), decrease the levels of proinflammatory cytokines (IL-17, IFN-g, TNF-a), and modulate the function of Tregs (14).…”

mentioning

confidence: 99%

Treatment of Experimental Autoimmune Encephalomyelitis by Sustained Delivery of Low-Dose IFN-α

Vásquez

Consuegra-Fernández

Aranda

et al. 2019

The Journal of Immunology

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic autoimmune disease with no curative treatment. The immune regulatory properties of type I IFNs have led to the approval of IFN-b for the treatment of relapsing-remitting MS. However, there is still an unmet need to improve the tolerability and efficacy of this therapy. In this work, we evaluated the sustained delivery of IFN-a1, either alone or fused to apolipoprotein A-1 by means of an adeno-associated viral (AAV) system in the mouse model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. These in vivo experiments demonstrated the prophylactic and therapeutic efficacy of the AAV-IFN-a or AAV-IFN-a fused to apolipoprotein A-1 vectors in experimental autoimmune encephalomyelitis, even at low doses devoid of hematological or neurologic toxicity. The sustained delivery of such low-dose IFN-a resulted in immunomodulatory effects, consisting of proinflammatory monocyte and T regulatory cell expansion. Moreover, encephalitogenic T lymphocytes from IFN-a-treated mice re-exposed to the myelin oligodendrocyte glycoprotein peptide in vitro showed a reduced proliferative response and cytokine (IL-17A and IFN-g) production, in addition to upregulation of immunosuppressive molecules, such as IL-10, IDO, or PD-1. In conclusion, the results of the present work support the potential of sustained delivery of low-dose IFN-a for the treatment of MS and likely other T cell-dependent chronic autoimmune disorders.

show abstract

IFN-β differentially regulates the function of T cell subsets in MS and EAE

Cited by 18 publications

References 102 publications

Inhibition of Type I Interferon Signaling abrogates Early Mycobacterium bovis Infection

Inhibition of Type I Interferon Signaling abrogates Early Mycobacterium bovis Infection

Inhibition of Type I Interferon Signaling Abrogates Early Mycobacterium bovis Infection

Treatment of Experimental Autoimmune Encephalomyelitis by Sustained Delivery of Low-Dose IFN-α

Contact Info

Product

Resources

About