 Your new post is loading...
Your new post is loading...
|
Scooped by
Gilbert C FAURE
June 17, 2017 8:26 AM
|
Rationale Interleukin (IL)-33, a new member of the IL-1 family, is constitutively expressed in epithelial tissues and lymphoid organs and plays an important role in the pathogenesis of allergic disease. However, the role of IL-33 in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unclear.
Objective To investigate the role of IL-33 in the pathophysiology of CRSwNP.
Methods We investigated IL-33 expression and its cellular origins in the nasal polyps (NPs) of human subjects by immunohistochemistry (IHC), quantitative reverse transcription PCR (qRT-PCR), and multiplex cytokine assays. Correlations between IL-33 expression and other inflammatory markers were also explored. To investigate the role of IL-33 in CRSwNP, anti-IL-33 antibody was used in a murine model of CRS.
Results Uncinate process tissues from control (19), CRSsNP (61), CRSwNP (69) and NP tissues (71) were used in this study. Increased expression of IL-33 mRNA and protein in patients with CRSwNP compared with controls was observed. The concentration of IL-33 protein in CRSwNP was positively correlated with the number of neutrophils and the expression of several Th1 and Th17 inflammatory markers, including interferon (IFN)-γ, IL-1β, tumour necrosis factor (TNF)-α, IL-17A, IL-22, and various markers for neutrophil recruitment. However, protein levels of IL-5 and quantity of eosinophils were inversely correlated with levels of IL-33. The expression of tissue inhibitor of metalloproteinase (TIMP)-1 was negatively correlated with IL-33 protein levels, while the expression of matrix metalloproteinase (MMP)-2 and MMP-9 was positively correlated with IL-33 protein levels. In animal studies, IL-33 expression was upregulated in the CRSwNP group compared with controls. Anti-IL-33 treatment reduced the thickness of oedematous mucosa, subepithelial collagen deposition, and infiltration of neutrophils, but infiltration of eosinophils was not reduced. This treatment also inhibited the expression of neutrophilic inflammatory cytokines, but not IL-4. In addition, the expression of intracellular adhesion molecule 1, vascular adhesion molecule 1 and CXCL-2 in the nasal mucosa was suppressed in mice treated with anti-IL-33 antibody.
Conclusions Our data suggest a role for IL-33 in the pathogenesis of CRSwNP via neutrophil recruitment. Therefore, anti-IL-33 may provide a new treatment strategy to target infiltrating neutrophils in CRSwNP.
|
|
Scooped by
Gilbert C FAURE
April 10, 2017 1:56 PM
|
The requirement of type I interferon (IFN) for natural killer (NK) cell activation in response to viral infection is known, but the underlying mechanism remains unclear. Here, we demonstrate that type I IFN signaling in inflammatory monocytes, but not in dendritic cells (DCs) or NK cells, is essential for NK cell function in response to a mucosal herpes simplex virus type 2 (HSV-2) infection. Mice deficient in type I IFN signaling, Ifnar−/− and Irf9−/− mice, had significantly lower levels of inflammatory monocytes, were deficient in IL-18 production, and lacked NK cell–derived IFN-γ. Depletion of inflammatory monocytes, but not DCs or other myeloid cells, resulted in lower levels of IL-18 and a complete abrogation of NK cell function in HSV-2 infection. Moreover, this resulted in higher susceptibility to HSV-2 infection. Although Il18−/− mice had normal levels of inflammatory monocytes, their NK cells were unresponsive to HSV-2 challenge. This study highlights the importance of type I IFN signaling in inflammatory monocytes and the induction of the early innate antiviral response.
|
|
Scooped by
Gilbert C FAURE
March 1, 2017 5:14 AM
|
J Interferon Cytokine Res. 2017 Feb;37(2):62-70. doi: 10.1089/jir.2016.0076.
|
|
Scooped by
Gilbert C FAURE
December 24, 2016 8:49 AM
|
J Interferon Cytokine Res. 2016 Apr;36(4):215-25. doi: 10.1089/jir.2015.0124. Epub 2016 Jan 27. Research Support, Non-U.S. Gov't; Review
Understanding the host immune response to vaginal exposure to RNA viruses is required to combat sexual transmission of this class of pathogens. In this study, using lymphocytic choriomeningitis virus (LCMV) and Zika virus (ZIKV) in wild-type mice, we show that these viruses replicate in the vaginal mucosa with minimal induction of antiviral interferon and inflammatory response, causing dampened innate-mediated control of viral replication and a failure to mature local antigen-presenting cells (APCs). Enhancement of innate-mediated inflammation in the vaginal mucosa rescues this phenotype and completely inhibits ZIKV replication. To gain a better understanding of how this dampened innate immune activation in the lower female reproductive tract may also affect adaptive immunity, we modeled CD8 T cell responses using vaginal LCMV infection. We show that the lack of APC maturation in the vaginal mucosa leads to a delay in CD8 T cell activation in the draining lymph node and hinders the timely appearance of effector CD8 T cells in vaginal mucosa, thus further delaying viral control in this tissue. Our study demonstrates that vaginal tissue is exceptionally vulnerable to infection by RNA viruses and provides a conceptual framework for the male to female sexual transmission observed during ZIKV infection.
Via Kenzibit
|
|
Scooped by
Gilbert C FAURE
June 3, 2016 9:50 AM
|
J Interferon Cytokine Res. 2015 Sep;35(9):682-9. doi: 10.1089/jir.2014.0123. Epub 2015 May 18. Research Support, Non-U.S. Gov't
|
|
Scooped by
Gilbert C FAURE
January 11, 2016 9:10 AM
|
Type I interferon (IFN) interferes with virus replication, promotes antiviral responses, and controls innate and adaptive immune responses to certain viruses.
|
Suggested by
Société Francaise d'Immunologie
November 22, 2015 1:29 PM
|
Mucosal Immunol. 2015 Nov 18. doi: 10.1038/mi.2015.110. [Epub ahead of print]
When activated by viral infection, plasmacytoid dendritic cells (pDCs) play a primary role in the immune response through secretion of IFN-α. Lactococcus lactis subsp.
Via Krishan Maggon
Intestinal microbial communities have profound effects on host physiology. Whereas the symbiotic contribution of commensal bacteria is well established, the role of eukaryotic viruses that are present in the gastrointestinal tract under homeostatic conditions is undefined. Here we demonstrate that a common enteric RNA virus can replace the beneficial function of commensal bacteria in the intestine. Murine norovirus (MNV) infection of germ-free or antibiotic-treated mice restored intestinal morphology and lymphocyte function without inducing overt inflammation and disease. The presence of MNV also suppressed an expansion of group 2 innate lymphoid cells observed in the absence of bacteria, and induced transcriptional changes in the intestine associated with immune development and type I interferon (IFN) signalling. Consistent with this observation, the IFN-[agr] receptor was essential for the ability of MNV to compensate for bacterial depletion. Importantly, MNV infection offset the deleterious effect of treatment with antibiotics in models of intestinal injury and pathogenic bacterial infection. These data indicate that eukaryotic viruses have the capacity to support intestinal homeostasis and shape mucosal immunity, similarly to commensal bacteria.
Via Dmitry Alexeev
|
|
Scooped by
Gilbert C FAURE
July 6, 2014 2:38 PM
|
Background:
Development and function of tissue resident mast cells (MCs) is tightly controlled by various cytokines, most of which belong to the typical T helper (Th) 2-type cytokines such as IL-3 and IL-4.
|
|
Scooped by
Gilbert C FAURE
January 29, 2014 2:42 AM
|
by Christoph Thelemann, Remzi Onur Eren, Manuel Coutaz, Jennifer Brasseit, Hanifa Bouzourene, Muriel Rosa, Anais Duval, Christine Lavanchy, Vanessa Mack, Christoph Mueller, Walter Reith, Hans Acha-Orbea Immune responses against intestinal...
|
|
|
Scooped by
Gilbert C FAURE
May 18, 2017 10:41 AM
|
The importance of IFNλs in the respiratory tract remains puzzling. Galani and colleagues
show that IFNλs provide front-line antiviral protection without activating inflammation.
When infection escapes IFNλ control, type I IFNs come into play to enhance antiviral
defenses and trigger pro-inflammatory responses essential for confronting infection
but causing immunopathology.
|
|
Scooped by
Gilbert C FAURE
March 8, 2017 1:47 PM
|
The requirement of type I interferon (IFN) for natural killer (NK) cell activation in response to viral infection is known, but the underlying mechanism remains unclear. Here, we demonstrate that type I IFN signaling in inflammatory monocytes, but not in dendritic cells (DCs) or NK cells, is essential for NK cell function in response to a mucosal herpes simplex virus type 2 (HSV-2) infection. Mice deficient in type I IFN signaling, Ifnar−/− and Irf9−/− mice, had significantly lower levels of inflammatory monocytes, were deficient in IL-18 production, and lacked NK cell–derived IFN-γ. Depletion of inflammatory monocytes, but not DCs or other myeloid cells, resulted in lower levels of IL-18 and a complete abrogation of NK cell function in HSV-2 infection. Moreover, this resulted in higher susceptibility to HSV-2 infection. Although Il18−/− mice had normal levels of inflammatory monocytes, their NK cells were unresponsive to HSV-2 challenge. This study highlights the importance of type I IFN signaling in inflammatory monocytes and the induction of the early innate antiviral response.
|
|
Scooped by
Gilbert C FAURE
December 27, 2016 8:40 AM
|
Lactic acid bacteria (LAB) form a major component of gut microbiota and are often used as probiotics for fermented foods, such as yoghurt. In this study, we aimed to evaluate immunomodulatory activity of LAB, especially that of Lactobacillus bulgaricus ME-552 (ME552) and Streptococcus thermophilus ME-553 (ME553). In vivo/in vitro assay was performed in order to investigate their effects on T cell function. After oral administration of ME553 to C57BL/6 mice, the amount of both interferon γ (IFN-γ) and interleukin 17 (IL-17) produced by cluster of differentiation (CD) 4+ T cells from Peyer’s patches (PPs) were significantly enhanced. On the other hand, ME552 only up-regulated the production of IL-17 from PP cells. The extent of induction for IFN-γ production differed between ME552 and ME553. These results suggest that LAB modulate T cell effector functions and mucosal immunity.
|
|
Suggested by
Société Francaise d'Immunologie
December 14, 2016 3:55 AM
|
|
|
Suggested by
Société Francaise d'Immunologie
November 20, 2016 12:54 PM
|
Suppressor of cytokine signaling 1 (SOCS1) is a negative feedback inhibitor of cytoplasmic Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling. SOCS1 also contains a nuclear localization sequence (NLS), yet the in vivo importance of nuclear translocation is unknown. We generated transgenic mice containing mutated Socs1ΔNLS that fails to translocate in the cell nucleus (MGLtg mice). Whereas mice fully deficient for SOCS1 die within the first three weeks due to excessive interferon signaling and multiorgan inflammation, mice expressing only non-nuclear Socs1ΔNLS (Socs1-/-MGLtg mice) were rescued from early lethality. Canonical interferon gamma signaling was still functional in Socs1-/-MGLtg mice as shown by unaltered tyrosine phosphorylation of STAT1 and whole genome expression analysis. However, a subset of NFB inducible genes was dysregulated. Socs1-/-MGLtg mice spontaneously developed low-grade inflammation in the lung and had elevated Th2-type cytokines. Upon ovalbumin sensitization and challenge, airway eosinophilia was increased in Socs1-/-MGLtg mice. Decreased transepithelial electrical resistance (TER) in trachea epithelial cells from Socs1-/-MGLtg mice suggests disrupted epithelial cell barrier. The results indicate that nuclear SOCS1 is a regulator of local immunity in the lung and unravel a so far unrecognized function for SOCS1 in the cell nucleus.
|
|
Scooped by
Gilbert C FAURE
February 25, 2016 7:57 AM
|
Mucosal Immunology is the official publication of the Society of Mucosal Immunology (SMI). It aims to provide a forum for both basic and clinical scientists to discuss all aspects of immunity and inflammation involving mucosal tissues.
|
|
Scooped by
Gilbert C FAURE
December 29, 2015 4:22 AM
|
Author Summary IAV causes seasonal epidemics that result in significant morbidity and mortality annually. Less frequently, novel viral strains emerge and are responsible for much larger outbreaks around the globe.
|
|
Scooped by
Gilbert C FAURE
March 13, 2015 3:27 PM
|
Ocular Surface Center, Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, 6565 Fannin Street, Houst
|
|
Suggested by
Société Francaise d'Immunologie
February 7, 2015 11:37 AM
|
Eur J Oral Sci. 2014 Jun;122(3):202-9. doi: 10.1111/eos.12131. Epub 2014 May 3. Comparative Study; Research Support, Non-U.S. Gov't
|
|
Scooped by
Gilbert C FAURE
August 28, 2014 4:16 AM
|
Internalization and TLR-dependent type I interferon production by monocytes in ...
|
|
Scooped by
Gilbert C FAURE
June 22, 2014 8:19 AM
|
T cells IL-9 breaks down barriers Nature.com Attenuated colitis in IL-9-deficient mice was associated with reduced production of tumour necrosis factor, interferon-γ and IL-21 by mucosal mononuclear cells, as well as lower levels of TH2-type...
|
|
Scooped by
Gilbert C FAURE
October 9, 2013 11:39 AM
|
A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumonia and acute respiratory distress syndrome and, apparently, from healthy poultry in March 2013 in Eastern China. We evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture system mimicking infection of the lower respiratory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients.
|
