Influenza Vaccination Induces NK-Cell-Mediated Type-II IFN Response that Regulates Humoral Immunity in an IL-6-Dependent Manner

Farsakoglu, Yagmur; Palomino‐Segura, Miguel; Latino, Irene; Zanaga, Silvia; Chatziandreou, Nikolaos; Pizzagalli, Diego Ulisse; Rinaldi, Andrea; Bolis, Marco; Sallusto, Federica; Stein, Jens V; González, Santiago F.

doi:10.1016/j.celrep.2019.01.104

Cited by 41 publications

(35 citation statements)

References 42 publications

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“…IL-6, as an important mediator of the acute phase response or as an anti-inflammatory cytokine, is secreted by macrophages to stimulate the immune response during infection. IL-6 induces intracellular signaling cascades that give rise to inflammatory cytokine production in inflammatory cells, such as neutrophils (van der Poll et al, 1997;Gao et al, 2018;Farsakoglu et al, 2019). In our study, PGPS induced neutrophil infiltration (Figure 1).…”

Section: Discussionsupporting

confidence: 50%

Role of Endoplasmic Reticulum Stress in Otitis Media

Zhao

Wang

et al. 2020

Front. Genet.

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Endoplasmic reticulum (ER) stress occurs in many inflammatory responses. Here, we investigated the role of ER stress and its associated apoptosis in otitis media (OM) to elucidate the mechanisms of OM and the signaling crosstalk between ER stress and other cell damage pathways, including inflammatory cytokines and apoptosis. We examined the expression of inflammatory cytokine-and ER stress-related genes by qRT-PCR, Western blotting, and immunohistochemistry (IHC) in the middle ear of C57BL/6J mice after challenge with peptidoglycan polysaccharide (PGPS), an agent inducing OM. We also evaluated the effect of the suppression of ER stress with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor. The study revealed the upregulation of ER stressand apoptosis-related gene expression after the PGPS treatment, specifically ATF6, CHOP, BIP, caspase-12, and caspase-3. TUDCA treatment of PGPS-treated mice decreased OM; reduced the expression of CHOP, BIP, and caspase 3; and significantly decreased the proinflammatory gene expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These results suggest that PGPS triggers ER stress and downstream proinflammatory gene expression in OM and that inhibition of ER stress alleviates OM. We propose that ER stress plays a critical role in inflammation and cell death, leading to the development of OM and points to ER stress inhibition as a potential therapeutic approach for the prevention of OM.

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Section: Discussionsupporting

confidence: 50%

Role of Endoplasmic Reticulum Stress in Otitis Media

Zhao

Wang

et al. 2020

Front. Genet.

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“…It has previously been shown that this proinflammatory cytokine is produced in vitro and in vivo in response to MVA in whole blood, PBMCs, primary human monocytes, and macrophages (27,28). IL-6 plays an important role in B-cell maturation, is closely associated with antibody production during infections and vaccination, and positively regulates the anti-influenza B-cell responses (24,(29)(30)(31)(32)(33). IL-6 is also considered a cytokine adjuvant that enhances immune response to vaccines (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

Immune Profiles Identification by Vaccinomics After MVA Immunization in Randomized Clinical Study

et al. 2020

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“…In humoral immunity, neutralizing antibodies can prevent the adsorption of the virus, via opsonization, and primarily interact with extracellular free viruses (Murasko et al, 2002). Activated Th1 cells release various cytokines (i.e., IFN-γ and TNF), activate macrophages and NK cells to induce further inflammatory reactions, and promote the proliferation and differentiation of cytotoxic T lymphocytes (CTLs), which play an important role in antiviral infection (Julkunen et al, 2001; Farsakoglu et al, 2019). However, studies have shown that while an inflammatory response helps to clear pathogens, excessive inflammatory reactions do not only protect the host organism but also cause the additional damage.…”

Section: Discussionmentioning

confidence: 99%

Insulin-Like Growth Factor 1 Regulates Acute Inflammatory Lung Injury Mediated by Influenza Virus Infection

Li¹,

Zhou²,

Zhang³

et al. 2019

Front. Microbiol.

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The acute inflammatory lung injury is an important cause of death due to influenza A virus (IAV) infection. Insulin-like growth factor 1 (IGF1) played an important role in the regulation of inflammation in the immune system. To investigate the role of IGF1 in IAV-mediated acute inflammatory lung injury, the expression of IGF1 and inflammatory cytokines was tested after IAV A/Puerto Rico/8/1934 (H1N1; abbreviated as PR8) infection in A549 cells. Then, a BALB/c mouse model of PR8 infection was established. On days 3, 5, 7, and 9 post-infection, the mice lung tissue was collected to detect the expression changes in IGF1 mRNA and protein. The mice were divided into four groups: (1) PBS (abbreviation of phosphate buffered saline); (2) PR8 + PBS; (3) PR8 + IGF1; and (4) PR8 + PPP (abbreviation of picropodophyllin, the IGF1 receptor inhibitor). The body weight and survival rate of the mice were monitored daily, and the clinical symptoms of the mice were recorded. On day 5 post-infection, the mice were sacrificed to obtain the serum and lung tissues. The expression of inflammatory cytokines in the serum was detected by enzyme linked immunosorbent assay; lung injury was observed by hematoxylin-eosin staining; the viral proliferation in the lung was detected by real-time quantitative PCR; and the protein expression of the main molecules in the phosphatidylinositol-3-kinases/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways was detected by Western blot. It was found that IGF1 expression is upregulated in A549 cells and BALB/c mice infected with PR8, whereas IGF1 regulated the expression of inflammatory cytokines induced by PR8 infection. Overexpression of IGF1 aggravated the IAV-mediated inflammatory response, whereas the inhibition of IGF1 receptor reduced such inflammatory response. The phosphorylation of IGF1 receptor triggered the PI3K/AKT and MAPK signaling pathways to induce an inflammatory response after IAV infection. Therefore, IGF1 plays an important immune function in IAV-mediated acute inflammatory lung injury. IGF1 may provide a therapeutic target for humans in response to an influenza outbreak, and inhibition of IGF1 or IGF1 receptor may represent a novel approach to influenza treatment.

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Influenza Vaccination Induces NK-Cell-Mediated Type-II IFN Response that Regulates Humoral Immunity in an IL-6-Dependent Manner

Cited by 41 publications

References 42 publications

Role of Endoplasmic Reticulum Stress in Otitis Media

Role of Endoplasmic Reticulum Stress in Otitis Media

Immune Profiles Identification by Vaccinomics After MVA Immunization in Randomized Clinical Study

Insulin-Like Growth Factor 1 Regulates Acute Inflammatory Lung Injury Mediated by Influenza Virus Infection

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