Punicalagin inhibits pro-inflammatory cytokines induced by influenza A virus

The exact role of innate immune cells upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and their contribution to the formation of the corona virus-induced disease (COVID)-19 associated cytokine storm is not yet fully understood. We show that human in vitro differentiated myeloid dendritic cells (mDC) as well as M1 and M2 macrophages are susceptible to infection with SARS-CoV-2 but are not productively infected. Furthermore, infected mDC, M1-, and M2 macrophages show only slight changes in their activation status. Surprisingly, none of the infected innate immune cells produced the pro-inflammatory cytokines interleukin (IL)−6, tumor necrosis factor (TNF)-α, or interferon (IFN)−α. Moreover, even in co-infection experiments using different stimuli, as well as non-influenza (non-flu) or influenza A (flu) viruses, only very minor IL-6 production was induced. In summary, we conclude that mDC and macrophages are unlikely the source of the first wave of cytokines upon infection with SARS-CoV-2.

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Inflammasomes and SARS-CoV-2 Infection

Viruses ◽

10.3390/v13122513 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2513

Author(s):

Juha Kaivola ◽

Tuula Anneli Nyman ◽

Sampsa Matikainen

Keyword(s):

Immune Response ◽

Inflammatory Cytokines ◽

Influenza A ◽

Protein Complexes ◽

Severe Disease ◽

Adaptive Immune Response ◽

Innate Immune ◽

Multiple Organs ◽

New Type ◽

Pro Inflammatory Cytokines

SARS-CoV-2 is a new type of coronavirus that has caused worldwide pandemic. The disease induced by SARS-CoV-2 is called COVID-19. A majority of people with COVID-19 have relatively mild respiratory symptoms. However, a small percentage of COVID-19 patients develop a severe disease where multiple organs are affected. These severe forms of SARS-CoV-2 infections are associated with excessive production of pro-inflammatory cytokines, so called “cytokine storm”. Inflammasomes, which are protein complexes of the innate immune system orchestrate development of local and systemic inflammation during virus infection. Recent data suggest involvement of inflammasomes in severe COVID-19. Activation of inflammasome exerts two major effects: it activates caspase-1-mediated processing and secretion of pro-inflammatory cytokines IL-1β and IL-18, and induces inflammatory cell death, pyroptosis, via protein called gasdermin D. Here, we provide comprehensive review of current understanding of the activation and possible functions of different inflammasome structures during SARS-CoV-2 infection and compare that to response caused by influenza A virus. We also discuss how novel SARS-CoV-2 mRNA vaccines activate innate immune response, which is a prerequisite for the activation of protective adaptive immune response.

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Acute Influenza A Virus Infection Affects Cell Cycle and Lineage Output of Hematopoietic Stem Cells

Blood ◽

10.1182/blood-2019-126482 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2467-2467

Author(s):

Marcel E G Rommel ◽

Lisa Walz ◽

Saskia Kohlscheen ◽

Franziska Schenk ◽

Yvonne Krebs ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Hematopoietic Stem Cells ◽

Influenza A Virus ◽

Inflammatory Cytokines ◽

Acute Phase ◽

Post Infection ◽

Influenza A ◽

Hematopoietic Stem ◽

The Impact

Long-term hematopoietic stem cells (LT-HSC) persist in quiescence to maintain their hematopoietic potential throughout life. In the case of need LT-HSC can be activated to replenish the pool of blood cells. We investigated the impact of acute influenza A virus (IAV) infection on hematopoiesis in C57Bl/6N mice, focusing on the most immature HSC and progenitors. Mice were infected with a lethal dose of IAV PR/8/1934 H1N1 (humane endpoints reached within 6 days post infection (dpi)). In two further groups, mice were treated daily with oseltamivir (antiviral neuraminidase inhibitor, dpi 0-4) or were vaccinated with single-cycle vesicular stomatitis virus replicon particles expressing a miss-matched neuraminidase from influenza A virus Yamaguchi/7/2004 H5N1 four weeks prior to infection. Both treatments rescued mice from infection-induced mortality. Every day 6-9 mice were analyzed for differences in the bone marrow (BM) and blood by flow cytometry and multiplex cytokine assays as well as in the lung to determine viral tissue titers and histopathology. HSC functionality was analyzed in a competitive BM transplantation of infected and non-infected mice. Irrespective of the treatment, high IAV lung tissue titers (≥5x106 tissue culture infectious dose 50) in the first days post infection (dpi 1-5) were associated with activation of HSC into the cell cycle. LT-HSCs (LSK, CD150+, CD34- and CD48-) were 50% less quiescent and shifted into the G1/S-G2-M phase (dpi 2-6) and returned to quiescence state after virus clearance (dpi 10). Furthermore, we detected 1.5-fold increase in proliferation of phenotypic LT-HSC. Differentiation was increased towards lymphoid progenitors (≥3-fold more compared to non-infected mice) during the acute phase of infection in untreated and oseltamivir treated mice and myeloid progenitors were reduced ~50% in all groups (dpi 4-8). We found the inflammatory cytokines IFNγ, IL-1α, IL-6, and TNFα to be significantly upregulated in the BM of untreated and oseltamivir treated mice but less in vaccinated animals (dpi 2-4). IL-1α or IL-6 stimulation of LT-HSCs was sufficient to initiate proliferation in cell culture. In all groups the initial drop of the peripheral platelet count (~30% lower compared to non-infected mice, dpi 2) was replenished with an excessive production of platelets (~45% increased, dpi 8-15). Histopathology and electron microscopy revealed the sequestration and accumulation of platelets in pulmonary capillaries and vessels. Subsequently, we detected twice as many mature megakaryocytes in the BM (dpi 2-4) and elevated CD41 expression on HSCs (LSK, CD150+ and CD34-; 3-fold more compared to non-infected mice dpi 2-6) indicating a myeloid/platelet-biased HSC compartment in response to infection. Competitive whole BM transplantation with activated LT-HSCs from the acute phase of infection vs non-infected mice showed delayed reconstitution of T-cells but a preferential differentiation towards platelets in recipient mice. Taken together, local IAV infection in the lung substantially affected LT-HSC quiescence and differentiation by inflammatory cytokines with systemic consequences and a myeloid/platelet-biased lineage output. Disclosures No relevant conflicts of interest to declare.

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Baicalin Downregulates RLRs Signaling Pathway to Control Influenza A Virus Infection and Improve the Prognosis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/4923062 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Peng Pang ◽

Ke Zheng ◽

Sizhi Wu ◽

Huachong Xu ◽

Li Deng ◽

...

Keyword(s):

Body Weight ◽

Inflammatory Response ◽

Signaling Pathway ◽

Influenza A Virus ◽

Inflammatory Cytokines ◽

Influenza A ◽

Body Weight Loss ◽

High Viral Load ◽

High Expression ◽

Key Factors

The objective of this study is to investigate the effects of baicalin on controlling the pulmonary infection and improving the prognosis in influenza A virus (IAV) infection. PCR and western blot were used to measure the changes of some key factors in RLRs signaling pathway. MSD electrochemiluminescence was used to measure the expression of pulmonary inflammatory cytokines including IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, and KC/GRO. Flow cytometry was used to detect the proportion of Th1, Th2, Th17, and Treg. The results showed that IAV infection led to low body weight and high viral load and high expression of RIG-I, IRF3, IRF7, and NF-κB mRNA, as well as RIG-I and NF-κB p65 protein. However, baicalin reduced the rate of body weight loss, inhibited virus replication, and downregulated the key factors of the RLRs signaling pathway. Besides, baicalin reduced the high expression inflammatory cytokines in lung and decreased the ratios of Th1/Th2 and Th17/Treg to arouse a brief but not overviolent inflammatory response. Therefore, baicalin activated a balanced host inflammatory response to limit immunopathologic injury, which was helpful to the improvement of clinical and survival outcomes.

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Production of interferon α and β, pro-inflammatory cytokines and the expression of suppressor of cytokine signaling (SOCS) in obese subjects infected with influenza A/H1N1

Clinical Nutrition ◽

10.1016/j.clnu.2013.10.011 ◽

2014 ◽

Vol 33 (5) ◽

pp. 922-926 ◽

Cited By ~ 13

Author(s):

Elí Terán-Cabanillas ◽

Maricela Montalvo-Corral ◽

Erika Silva-Campa ◽

Graciela Caire-Juvera ◽

Silvia Y. Moya-Camarena ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Influenza A ◽

Cytokine Signaling ◽

Interferon Α ◽

Suppressor Of Cytokine Signaling ◽

Influenza A H1n1 ◽

Obese Subjects ◽

Pro Inflammatory Cytokines

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The Effect of a Lipopolysaccharide from Rhodobacter capsulatus PG on Inflammation Caused by Various Influenza Strains

Acta Naturae ◽

10.32607/20758251-2019-11-3-46-55 ◽

2019 ◽

Vol 11 (3) ◽

pp. 46-55

Author(s):

S. V. Zubova ◽

M. F. Vorovich ◽

A. S. Gambaryan ◽

A. A. Ishmukhametov ◽

S. V. Grachev ◽

...

Keyword(s):

Body Weight ◽

Influenza Virus ◽

Blood Serum ◽

Influenza A Virus ◽

Inflammatory Cytokines ◽

Influenza A ◽

Rhodobacter Capsulatus ◽

Igg Antibodies ◽

Anti Inflammatory ◽

Virus Strains

The development of a specific inflammation in mice that had been infected by two influenza virus strains, A/chicken/Kurgan/5/2005 (H5N1) and A/Hamburg/2009 MA (H1N1), was studied. We investigated the effect of a non-toxic lipopolysaccharide from Rhodobacter capsulatus PG on the survival and body weight of the mice, production of IgG antibodies, and the induction of pro- and anti-inflammatory cytokines in blood serum. The administration of the R. capsulatus PG lipopolysaccharide was shown to induce interferon- synthesis, both in healthy and influenza A virus-infected mice, and to promote production of antiviral antibodies in the blood of the influenza-infected animals.

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SARS-CoV-2 causes a different cytokine response compared to other cytokine storm-causing respiratory viruses in severely ill patients

10.1101/2020.11.14.20231878 ◽

2020 ◽

Author(s):

Marton Olbei ◽

Isabelle Hautefort ◽

Dezso Modos ◽

Agatha Treveil ◽

Martina Poletti ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Influenza A ◽

Feedback Loop ◽

Cytokine Storm ◽

Viral Pathogens ◽

Adaptive Immune ◽

Adaptive Immune Cells ◽

Cytokine Levels ◽

Key Aspects ◽

Pro Inflammatory Cytokines

AbstractHyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS) is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells are activated, and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with COVID-19 for a subgroup of patients. CRS is not unique to SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, H7N9). Here, we collected changing cytokine levels upon infection with the aforementioned viral pathogens through a comprehensive literature search. We analysed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. A map of such responses could help specialists identify interventions that successfully alleviated CRS in different diseases and evaluate whether they could be used in COVID-19 cases.

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SARS-CoV-2 Causes a Different Cytokine Response Compared to Other Cytokine Storm-Causing Respiratory Viruses in Severely Ill Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.629193 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marton Olbei ◽

Isabelle Hautefort ◽

Dezso Modos ◽

Agatha Treveil ◽

Martina Poletti ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Influenza A ◽

Respiratory Viruses ◽

Cytokine Response ◽

Type I ◽

Cytokine Storm ◽

Cytokine Responses ◽

Adaptive Immune Cells ◽

Key Aspects ◽

Pro Inflammatory Cytokines

Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with coronavirus 2019 (COVID-19) for a subgroup of patients. CRS is not unique to the SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, and H7N9). With a comprehensive literature search, we collected changing the cytokine levels from patients upon infection with the viral pathogens mentioned above. We analyzed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. Our curation indicates that the cytokine response induced by SARS-CoV-2 is different compared to other CRS-causing respiratory viruses, as SARS-CoV-2 does not always induce specific cytokines like other coronaviruses or influenza do, such as IL-2, IL-10, IL-4, or IL-5. Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.

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