Respiratory macrophages and dendritic cells mediate respiratory syncytial virus-induced IL-33 production in TLR3- or TLR7-dependent manner

Qi, Feifei; Wang, Dandan; Liu, Jing; Zhang, Sheng; Liu, Xu; Hu, Haiyan; Liu, Beixing

doi:10.1016/j.intimp.2015.10.022

Cited by 34 publications

(38 citation statements)

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“…P-values < 0·05 were considered significant; n.d. = not detected. macrophages and dendritic cells produced interleukin (IL)-33 induced by TLR-7 activation in the respiratory tract of respiratory syncytial virus ssRNA-infected mice [21]. These findings strongly suggest the dominance of TLR-7 with respect to the provocation of inflammation in LSGs.…”

Section: Discussionmentioning

confidence: 80%

“…It was reported that single-strand RNA (ssRNA) as a TLR-7 ligand was recognized by TLR-7 but not TLR-8 and activated the transcription of TNF-α in synovial tissues from rheumatoid arthritis patients, suggesting that the activation of TLR-7 was more closely associated with inflammation compared to TLR-8 activation [20]. macrophages and dendritic cells produced interleukin (IL)-33 induced by TLR-7 activation in the respiratory tract of respiratory syncytial virus ssRNA-infected mice [21]. Alveolar The expressions of IFN-α and TLR-7 in CD123 + CD303 + pDCs from pSS patients (n = 6) stimulated with 1 mM loxoribine for 6 h and/or 1000 U/ml IFN-β for 12 h, analyzed by flow cytometry.…”

Section: Discussionmentioning

confidence: 99%

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Activation of Toll‐like receptor 7 signaling in labial salivary glands of primary Sjögren's syndrome patients

et al. 2018

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The aim of this study was to determine the expressions of Toll-like receptors (TLRs) 7-9 and type I interferon (IFN) signal in labial salivary glands (LSGs) and cultured salivary gland epithelial cells (SGECs) from primary Sjögren's syndrome (pSS) patients. We performed an immunohistochemistry analysis of LSGs from 11 patients with pSS as defined by American-European Consensus Group classification criteria and five healthy subjects. The pSS patients' SGECs were analyzed by immunofluorescence and western blotting. IFN-α expression was examined by immunosorbent assay and flow cytometry. Mononuclear cells (MNCs) from pSS patients' LSGs showed TLR-7-dominant expression. B cells, plasma cells and plasmacytoid dendritic cells (pDCs) co-expressed with TLR-7.Myeloid differentiation primary response gene 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6) and interferon regulatory factor 7 (IRF7) co-expressed with the pDC marker CD303 in LSGs. Ducts from pSS patients dominantly expressed TLR-7, and TLR-7 in the ducts coexpressed with MyD88, TRAF6 and IRF7. Type I IFNs including IFN-α and IFN-β were detected in MNCs and ducts in pSS patients' LSGs. Increased TRAF6 expression and the nuclear translocation of IRF7 in SGECs were detected by immunofluorescence following loxoribine (a TLR-7 ligand) stimulation despite IFN-β pretreatment. Western blotting showed increased TRAF6 expression in SGECs following IFN-β and loxoribine stimulation. Although no increase in IFN-α was detected in supernatant from stimulated SGECs, the IFN-α in supernatant from stimulated peripheral blood pDCs from pSS patients was significantly increased. Our findings suggest that TLR-7 is dominantly expressed in both MNCs and ducts with downstream signals for type I IFNs, indicating that TLR7-dominant innate immunity is related to the development of sialadenitis in pSS.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Activation of Toll‐like receptor 7 signaling in labial salivary glands of primary Sjögren's syndrome patients

et al. 2018

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“…Although previous study has implicated type-2 pneumocytes and other structural cells as the major producers of IL-33 in the lungs, 43 other studies have detected IL-33 in myeloid cells under various allergen challenge and during viral infection. 25,28,44 Moreover, a recent study in Il33-driven citrine reporter mice have demonstrated that CD45 + cells expressed low levels of IL-33 at steady-state, and allergen exposure augmented its expression. 45 In the present study, we observed that RSV-induced IL-33 expression in both myeloid and lung structural cells.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary IL‐33 orchestrates innate immune cells to mediate respiratory syncytial virus‐evoked airway hyperreactivity and eosinophilia

Lai

Chi

et al. 2019

Allergy

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Background: Respiratory syncytial virus (RSV) infection is epidemiologically linked to asthma. During RSV infection, IL-33 is elevated and promotes immune cell activation, leading to the development of asthma. However, which immune cells are responsible for triggering airway hyperreactivity (AHR), inflammation and eosinophilia remained to be clarified. We aimed to elucidate the individual roles of IL-33-activated innate immune cells, including ILC2s and ST2 + myeloid cells, in RSV infection-triggered pathophysiology. Methods:The role of IL-33/ILC2 axis in RSV-induced AHR inflammation and eosinophilia were evaluated in the IL-33-deficient and YetCre-13 Rosa-DTA mice. Myeloidspecific, IL-33-deficient or ST2-deficient mice were employed to examine the role of IL-33 and ST2 signaling in myeloid cells. Results:We found that IL-33-activated ILC2s were crucial for the development of AHR and airway inflammation, during RSV infection. ILC2-derived IL-13 was sufficient for RSV-driven AHR, since reconstitution of wild-type ILC2 rescued RSV-driven AHR in IL-13-deficient mice. Meanwhile, myeloid cell-derived IL-33 was required for airway inflammation, ST2 + myeloid cells contributed to exacerbation of airway inflammation, suggesting the importance of IL-33 signaling in these cells. Local and peripheral eosinophilia is linked to both ILC2 and myeloid IL-33 signaling. Conclusions:This study highlights the importance of IL-33-activated ILC2s in mediating RSV-triggered AHR and eosinophilia. In addition, IL-33 signaling in myeloid cells is crucial for airway inflammation. K E Y W O R D S asthma, eosinophilia, IL-33, ILC2, respiratory syncytial virus | 819 WU et al.

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“…This epidemiological study found that newborn infants had increased susceptibility to RSV because they did not have fully functioning pDCs and therefore there was low IFN induction by RIG-I (Marr et al, 2014). Respiratory macrophages and pDCs are critical in combating RSV infection, not only through RLR signaling, but also through TLR3-and TLR7-mediated mechanisms (Qi et al, 2015). Using mouse pneumonia virus, the rodent-specific form of RSV, it was shown that TLR7 was critical for the host defense response and IFN induction during infection (Davidson et al, 2011).…”

Section: Rna Nucleic Acid Sensing In Viral Immunology and Autoimmunitymentioning

confidence: 99%

The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders

Matz

Guzman

Goodman

2019

Nucleic Acid Sensing and Immunity - Part B

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Innate immunity, the first line of defense against invading pathogens, is an ancient form of host defense found in all animals, from sponges to humans. During infection, innate immune receptors recognize conserved molecular patterns, such as microbial surface molecules, metabolites produces during infection, or nucleic acids of the microbe’s genome. When initiated, the innate immune response activates a host defense program that leads to the synthesis proteins capable of pathogen killing. In mammals, the induction of cytokines during the innate immune response leads to the recruitment of professional immune cells to the site of infection, leading to an adaptive immune response. While a fully functional innate immune response is crucial for a proper host response and curbing microbial infection, if the innate immune response is dysfunctional and is activated in the absence of infection, autoinflammation and autoimmune disorders can develop. Therefore, it follows that the innate immune response must be tightly controlled to avoid an autoimmune response from host-derived molecules, yet still unencumbered to respond to infection. In this review, we will focus on the innate immune response activated from cytosolic nucleic acids, derived from the microbe or host itself. We will depict how viruses and bacteria activate these nucleic acid sensing pathways and their mechanisms to inhibit the pathways. We will also describe the autoinflammatory and autoimmune disorders that develop when these pathways are hyperactive. Finally, we will discuss gaps in knowledge with regard to innate immune response failure and identify where further research is needed.

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Respiratory macrophages and dendritic cells mediate respiratory syncytial virus-induced IL-33 production in TLR3- or TLR7-dependent manner

Cited by 34 publications

References 36 publications

Activation of Toll‐like receptor 7 signaling in labial salivary glands of primary Sjögren's syndrome patients

Activation of Toll‐like receptor 7 signaling in labial salivary glands of primary Sjögren's syndrome patients

Pulmonary IL‐33 orchestrates innate immune cells to mediate respiratory syncytial virus‐evoked airway hyperreactivity and eosinophilia

The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders

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