Absence of SP-A modulates innate and adaptive defense responses to pulmonary influenza infection

2002 ◽  
Vol 282 (3) ◽  
pp. L563-L572 ◽  
Author(s):  
Ann Marie LeVine ◽  
Kevan Hartshorn ◽  
James Elliott ◽  
Jeffrey Whitsett ◽  
Thomas Korfhagen
Keyword(s):  
Lung Inflammation ◽  
Influenza A ◽  
Influenza Infection ◽  
Pulmonary Inflammation ◽  
Defense Responses ◽  
Interferon Γ ◽  
Viral Clearance ◽  
Myeloperoxidase Activity ◽  
Respiratory Pathogens ◽  
Innate Defense

Mice lacking surfactant protein SP-A [SP-A(−/−)] and wild type SP-A(+/+) mice were infected with influenza A virus (IAV) by intranasal instillation. Decreased clearance of IAV was observed in SP-A(−/−) mice and was associated with increased pulmonary inflammation. Treatment of SP-A(−/−) mice with exogenous SP-A enhanced viral clearance and decreased lung inflammation. Uptake of IAV by alveolar macrophages was similar in SP-A(−/−) and SP-A(+/+) mice. Myeloperoxidase activity was reduced in isolated bronchoalveolar lavage neutrophils from SP-A(−/−) mice. B lymphocytes and activated T lymphocytes were increased in the lung and spleen, whereas T helper (Th) 1 responses were increased [interferon-γ, interleukin (IL)-2, and IgG2a] and Th2 responses were decreased (IL-4, and IL-10, and IgG1) in the lungs of SP-A(−/−) mice 7 days after IAV infection. In the absence of SP-A, impaired viral clearance was associated with increased lung inflammation, decreased neutrophil myeloperoxidase activity, and increased Th1 responses. Because the airway is the usual portal of entry for IAV and other respiratory pathogens, SP-A is likely to play a role in innate defense and adaptive immune responses to IAV.

scholarly journals Topical exposure to triclosan inhibits Th1 immune responses and reduces T cells responding to influenza infection in mice

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244436
Author(s):  
Hillary L. Shane ◽  
Sreekumar Othumpangat ◽  
Nikki B. Marshall ◽  
Francoise Blachere ◽  
Ewa Lukomska ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Healthcare Workers ◽  
Influenza A ◽  
Influenza Infection ◽  
Statistical Significance ◽  
Lethal Dose ◽  
Respiratory Pathogens ◽  
Increased Risk

Healthcare workers concurrently may be at a higher risk of developing respiratory infections and allergic disease, such as asthma, than the general public. Increased incidence of allergic diseases is thought to be caused, in part, due to occupational exposure to chemicals that induce or augment Th2 immune responses. However, whether exposure to these chemical antimicrobials can influence immune responses to respiratory pathogens is unknown. Here, we use a BALB/c murine model to test if the Th2-promoting antimicrobial chemical triclosan influences immune responses to influenza A virus. Mice were dermally exposed to 2% triclosan for 7 days prior to infection with a sub-lethal dose of mouse adapted PR8 A(H1N1) virus (50 pfu); triclosan exposure continued until 10 days post infection (dpi). Infected mice exposed to triclosan did not show an increase in morbidity or mortality, and viral titers were unchanged. Assessment of T cell responses at 10 dpi showed a decrease in the number of total and activated (CD44hi) CD4+ and CD8+ T cells at the site of infection (BAL and lung) in triclosan exposed mice compared to controls. Influenza-specific CD4+ and CD8+ T cells were assessed using MHCI and MHCII tetramers, with reduced populations, although not reaching statistical significance at these sites following triclosan exposure. Reductions in the Th1 transcription factor T-bet were seen in both activated and tetramer+ CD4+ and CD8+ T cells in the lungs of triclosan exposed infected mice, indicating reduced Th1 polarization and providing a potential mechanism for numerical reduction in T cells. Overall, these results indicate that the immune environment induced by triclosan exposure has the potential to influence the developing immune response to a respiratory viral infection and may have implications for healthcare workers who may be at an increased risk for developing infectious diseases.

scholarly journals ATP catabolism by tissue nonspecific alkaline phosphatase contributes to development of ARDS in influenza-infected mice

2018 ◽  
Vol 314 (1) ◽  
pp. L83-L92 ◽  
Author(s):  
Parker S. Woods ◽  
Lauren M. Doolittle ◽  
Judy M. Hickman-Davis ◽  
Ian C. Davis
Keyword(s):  
Alkaline Phosphatase ◽  
Influenza A ◽  
Influenza Infection ◽  
High Capacity ◽  
Receptor Activation ◽  
Respiratory Pathogens ◽  
Influenza A Viruses ◽  
Epithelial Barrier Function ◽  
Lung Dysfunction ◽  
Tissue Nonspecific Alkaline Phosphatase

Influenza A viruses are highly contagious respiratory pathogens that are responsible for significant morbidity and mortality worldwide on an annual basis. We have shown previously that influenza infection of mice leads to increased ATP and adenosine accumulation in the airway lumen. Moreover, we demonstrated that A1-adenosine receptor activation contributes significantly to influenza-induced acute respiratory distress syndrome (ARDS). However, we found that development of ARDS in influenza-infected mice does not require catabolism of ATP to adenosine by ecto-5′-nucleotidase (CD73). Hence, we hypothesized that increased adenosine generation in response to infection is mediated by tissue nonspecific alkaline phosphatase (TNAP), which is a low-affinity, high-capacity enzyme that catabolizes nucleotides in a nonspecific manner. In the current study, we found that whole lung and BALF TNAP expression and alkaline phosphatase enzymatic activity increased as early as 2 days postinfection (dpi) of C57BL/6 mice with 10,000 pfu/mouse of influenza A/WSN/33 (H1N1). Treatment at 2 and 4 dpi with a highly specific quinolinyl-benzenesulfonamide TNAP inhibitor (TNAPi) significantly reduced whole lung alkaline phosphatase activity at 6 dpi but did not alter TNAP gene or protein expression. TNAPi treatment attenuated hypoxemia, lung dysfunction, histopathology, and pulmonary edema at 6 dpi without impacting viral replication or BALF adenosine. Treatment also improved epithelial barrier function and attenuated cellular and humoral immune responses to influenza infection. These data indicate that TNAP inhibition can attenuate influenza-induced ARDS by reducing inflammation and fluid accumulation within the lung. They also further emphasize the importance of adenosine generation for development of ARDS in influenza-infected mice.

scholarly journals Selective deletion of SHIP-1 in hematopoietic cells in mice leads to severe lung inflammation involving ILC2 cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xujun Ye ◽  
Fengrui Zhang ◽  
Li Zhou ◽  
Yadong Wei ◽  
Li Zhang ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Airway Remodeling ◽  
Pulmonary Inflammation ◽  
Hematopoietic Cells ◽  
Cell Lineage ◽  
Allergic Inflammation ◽  
Cell Types ◽  
Lymphoid Cells ◽  
Whole Body

AbstractSrc homology 2 domain–containing inositol 5-phosphatase 1 (SHIP-1) regulates the intracellular levels of phosphotidylinositol-3, 4, 5-trisphosphate, a phosphoinositide 3–kinase (PI3K) product. Emerging evidence suggests that the PI3K pathway is involved in allergic inflammation in the lung. Germline or induced whole-body deletion of SHIP-1 in mice led to spontaneous type 2-dominated pulmonary inflammation, demonstrating that SHIP-1 is essential for lung homeostasis. However, the mechanisms by which SHIP-1 regulates lung inflammation and the responsible cell types are still unclear. Deletion of SHIP-1 selectively in B cells, T cells, dendritic cells (DC) or macrophages did not lead to spontaneous allergic inflammation in mice, suggesting that innate immune cells, particularly group 2 innate lymphoid cells (ILC2 cells) may play an important role in this process. We tested this idea using mice with deletion of SHIP-1 in the hematopoietic cell lineage and examined the changes in ILC2 cells. Conditional deletion of SHIP-1 in hematopoietic cells in Tek-Cre/SHIP-1 mice resulted in spontaneous pulmonary inflammation with features of type 2 immune responses and airway remodeling like those seen in mice with global deletion of SHIP-1. Furthermore, when compared to wild-type control mice, Tek-Cre/SHIP-1 mice displayed a significant increase in the number of IL-5/IL-13 producing ILC2 cells in the lung at baseline and after stimulation by allergen Papain. These findings provide some hints that PI3K signaling may play a role in ILC2 cell development at baseline and in response to allergen stimulation. SHIP-1 is required for maintaining lung homeostasis potentially by restraining ILC2 cells and type 2 inflammation.

scholarly journals Differential Expression of Serum Exosome microRNAs and Cytokines in Influenza A and B Patients Collected in the 2016 and 2017 Influenza Seasons

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 149
Author(s):  
Sreekumar Othumpangat ◽  
William G. Lindsley ◽  
Donald H. Beezhold ◽  
Michael L. Kashon ◽  
Carmen N. Burrell ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Influenza A ◽  
Influenza Infection ◽  
Cell Types ◽  
Airway Epithelial Cells ◽  
Differentially Expressed ◽  
Influenza B ◽  
Airway Epithelial ◽  
Monocyte Chemoattractant Protein 1 ◽  
Novel Approach

MicroRNAs (miRNAs) have remarkable stability and are key regulators of mRNA transcripts for several essential proteins required for the survival of cells and replication of the virus. Exosomes are thought to play an essential role in intercellular communications by transporting proteins and miRNAs, making them ideal in the search for biomarkers. Evidence suggests that miRNAs are involved in the regulation of influenza virus replication in many cell types. During the 2016 and 2017 influenza season, we collected blood samples from 54 patients infected with influenza and from 30 healthy volunteers to identify the potential role of circulating serum miRNAs and cytokines in influenza infection. Data comparing the exosomal miRNAs in patients with influenza B to healthy volunteers showed 76 miRNAs that were differentially expressed (p < 0.05). In contrast, 26 miRNAs were differentially expressed between patients with influenza A (p < 0.05) and the controls. Of these miRNAs, 11 were commonly expressed in both the influenza A and B patients. Interferon (IFN)-inducing protein 10 (IP-10), which is involved in IFN synthesis during influenza infection, showed the highest level of expression in both influenza A and B patients. Influenza A patients showed increased expression of IFNα, GM-CSF, interleukin (IL)-13, IL-17A, IL-1β, IL-6 and TNFα, while influenza B induced increased levels of EGF, G-CSF, IL-1α, MIP-1α, and TNF-β. In addition, hsa-miR-326, hsa-miR-15b-5p, hsa-miR-885, hsa-miR-122-5p, hsa-miR-133a-3p, and hsa-miR-150-5p showed high correlations to IL-6, IL-15, IL-17A, IL-1β, and monocyte chemoattractant protein-1 (MCP-1) with both strains of influenza. Next-generation sequencing studies of H1N1-infected human lung small airway epithelial cells also showed similar pattern of expression of miR-375-5p, miR-143-3p, 199a-3p, and miR-199a-5p compared to influenza A patients. In summary, this study provides insights into the miRNA profiling in both influenza A and B virus in circulation and a novel approach to identify the early infections through a combination of cytokines and miRNA expression.

scholarly journals The Effects of Social Distancing Policies on non-SARS-CoV-2 Respiratory Pathogens

2021 ◽  
Author(s):  
Jeff Nawrocki ◽  
Katherine Olin ◽  
Martin C Holdrege ◽  
Joel Hartsell ◽  
Lindsay Meyers ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza A ◽  
Detection Rate ◽  
Respiratory Illness ◽  
Respiratory Pathogens ◽  
Public Health Response ◽  
Mixed Effect ◽  
Detection Rates ◽  
Social Distancing ◽  
The Impact

Abstract Background The initial focus of the US public health response to COVID-19 was the implementation of numerous social distancing policies. While COVID-19 was the impetus for imposing these policies, it is not the only respiratory disease affected by their implementation. This study aimed to assess the impact of social distancing policies on non-SARS-CoV-2 respiratory pathogens typically circulating across multiple US states. Methods Linear mixed-effect models were implemented to explore the effects of five social distancing policies on non-SARS-CoV-2 respiratory pathogens across nine states from January 1 through May 1, 2020. The observed 2020 pathogen detection rates were compared week-by-week to historical rates to determine when the detection rates were different. Results Model results indicate that several social distancing policies were associated with a reduction in total detection rate, by nearly 15%. Policies were associated with decreases in pathogen circulation of human rhinovirus/enterovirus and human metapneumovirus, as well as influenza A, which typically decrease after winter. Parainfluenza viruses failed to circulate at historical levels during the spring. Total detection rate in April 2020 was 35% less than historical average. Many of the pathogens driving this difference fell below historical detection rate ranges within two weeks of initial policy implementation. Conclusion This analysis investigated the effect of multiple social distancing policies implemented to reduce transmission of SARS-CoV-2 on non-SARS-CoV-2 respiratory pathogens. These findings suggest that social distancing policies may be used as an impactful public health tool to reduce communicable respiratory illness.

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