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Phenol-soluble modulin peptides contribute to influenza-associated Staphylococcus aureus pneumonia.

Tue, 09/19/2017 - 16:00
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Phenol-soluble modulin peptides contribute to influenza-associated Staphylococcus aureus pneumonia.

Infect Immun. 2017 Sep 11;:

Authors: Bloes DA, Haasbach E, Hartmayer C, Hertlein T, Klingel K, Kretschmer D, Planz O, Peschel A

Abstract
Influenza A virus (IAV) infections are often followed by secondary bacterial lung infection, which is a major reason for severe, often fatal pneumonia. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains such as USA300 cause particularly severe and difficult-to-treat cases of IAV-associated pneumonia. CA-MRSA are known to produce extraordinarily high amounts of phenol-soluble modulin (PSM) peptides, important cytotoxins and proinflammatory molecules contributing to several types of S. aureus infection. However, their potential role in pneumonia has remained elusive. We determined the impact of PSMs on human lung epithelial cells and found that PSMs are cytotoxic and induce secretion of the proinflammatory cytokine IL-8 in these cells. Both effects were boosted by prior infection with 2009's swine flu pandemic IAV strain H1N1 suggesting that PSMs may contribute to lung inflammation and damage in IAV-associated S. aureus pneumonia. Notably, PSM-producing USA300 caused higher mortality than an isogenic PSM-deficient mutant in a mouse IAV/S. aureus pneumonia co-infection model indicating that PSMs are major virulence factors in IAV-associated S. aureus pneumonia and may represent important targets for future anti-infective therapies.

PMID: 28893917 [PubMed - as supplied by publisher]

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Epidemiological features of influenza circulation in swine populations: A systematic review and meta-analysis.

Tue, 09/19/2017 - 16:00
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Epidemiological features of influenza circulation in swine populations: A systematic review and meta-analysis.

PLoS One. 2017;12(6):e0179044

Authors: Baudon E, Peyre M, Peiris M, Cowling BJ

Abstract
BACKGROUND: The emergence of the 2009 influenza pandemic virus with a swine origin stressed the importance of improving influenza surveillance in swine populations. The objectives of this systematic review and meta-analysis were to describe epidemiological features of swine influenza (SI) across the world and identify factors impacting swine influenza virus surveillance.
METHODS: The systematic review followed the PRISMA guidelines. Articles published after 1990 containing data on SI on pig and herd-level seroprevalence, isolation and detection rates, and risk factors were included. Meta-regression analyses using seroprevalence and virological rates were performed.
RESULTS: A total of 217 articles were included. Low avian influenza (AI) seroprevalence (means pig = 4.1%; herd = 15%) was found, showing that AIV do not readily establish themselves in swine while SIV seroprevalence was usually high across continents (influenza A means pig = 32.6-87.8%; herd = 29.3-100%). Higher pig density and number of pigs per farm were shown by the meta-regression analyses and/or the risk factor articles to be associated with higher SI seroprevalence. Lower seroprevalence levels were observed for countries with low-to-medium GDP. These results suggest that larger industrial farms could be more at risk of SIV circulation. Sampling swine with influenza-like illness (ILI) was positively associated with higher isolation rates; most studies in Europe, Latin and North America were targeting swine with ILI.
CONCLUSIONS: To improve understanding of SI epidemiology, standardization of the design and reporting of SI epidemiological studies is desirable. Performance of SI surveillance systems in low-to-medium GDP countries should be evaluated to rule out technical issues linked to lower observed SIV prevalence. Targeting certain swine age groups, farming systems and swine with ILI may improve the surveillance cost-effectiveness. However, focusing on pigs with ILI may bias virus detection against strains less virulent for swine but which may be important as pandemic threats.

PMID: 28591202 [PubMed - indexed for MEDLINE]

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Natural STING Agonist as an "Ideal" Adjuvant for Cutaneous Vaccination.

Tue, 09/19/2017 - 16:00
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Natural STING Agonist as an "Ideal" Adjuvant for Cutaneous Vaccination.

J Invest Dermatol. 2016 Nov;136(11):2183-2191

Authors: Wang J, Li P, Wu MX

Abstract
A potent adjuvant that induces strong protective immunity without incurring any significant skin reactogenicity is urgently needed for cutaneous vaccination. Here, we report that a natural agonist of stimulator of interferon genes (STING), 2'3'- cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), robustly augmented and prolonged the cellular and humoral immune responses provoked by H5N1 and 2009 H1N1 pandemic influenza vaccines after a single dose of intradermal, but not intramuscular, immunization. The potency of cGAMP for cutaneous vaccination was ascribed to a large number of antigen-presenting cells resident in the skin and ready for immediate activation when cGAMP was injected. However, its potency was severely compromised in the muscle, because antigen-presenting cells could not be promptly recruited to the injection site before the injected cGAMP was diffused out. The superior adjuvant effect and safety of cGAMP were also confirmed in a more clinically relevant swine model of skin. The vigorous immune responses elicited by cGAMP with no overt skin irritation was attributable to its stay in the skin, which was brief but sufficient to activate dermal dendritic cells. This small and well-characterized self-molecule holds great promise as an ideal adjuvant for cutaneous vaccination.

PMID: 27287182 [PubMed - indexed for MEDLINE]

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