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Staphylococcus aureus specific lung resident memory CD4⁺ Th1 cells attenuate the severity of influenza virus induced secondary bacterial pneumonia.

ABSTRACT: Staphylococcus aureus is a major cause of severe pulmonary infections. The evolution of multi-drug resistant strains limits antibiotic treatment options. To date, all candidate vaccines tested have failed, highlighting the need for an increased understanding of the immunological requirements for effective S. aureus immunity. Using an S. aureus strain engineered to express a trackable CD4⁺ T cell epitope and a murine model of S. aureus pneumonia, we show strategies that lodge Th1 polarised bacterium specific CD4⁺ tissue resident memory T cells (Trm) in the lung can significantly attenuate the severity of S. aureus pneumonia. This contrasts natural infection of mice that fails to lodge CD4⁺ Trm cells along the respiratory tract or provide protection against re-infection, despite initially generating Th17 bacterium specific CD4⁺ T cell responses. Interestingly, lack of CD4⁺ Trm formation after natural infection in mice appears to be reflected in humans, where the frequency of S. aureus reactive CD4⁺ Trm cells in lung tissue is also low. Our findings reveal the protective capacity of S. aureus specific respiratory tract CD4⁺ Th1 polarised Trm cells and highlight the potential for targeting these cells in vaccines that aim to prevent the development of S. aureus pneumonia.

SUBMITTER: Braverman J

PROVIDER: S-EPMC9148937 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Our objective was to illustrate the potential of metabolomics to identify novel biomarkers of illness severity in a child with fatal necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). We present a case report with two control groups and a metabolomics analysis: an infant with fatal MRSA pneumonia, four children with influenza pneumonia (pneumonia control group), and seven healthy children with no known infections (healthy control group). Urine samples were collected from all children. Metabolites were identified and quantified using 1 H-nuclear magnetic resonance spectrometry. Normalized metabolite concentration data from children with influenza pneumonia and healthy controls were compared by using an unpaired Student t test. To identify differentiating metabolites of MRSA pneumonia, the fold change of each metabolite was calculated by dividing each urine metabolite concentration of the patient with fatal MRSA pneumonia by the median urine concentration values of the same metabolite of the patients with influenza pneumonia and healthy controls, respectively. MetScape (http://metscape.ncibi.org/), a bioinformatics tool, was used for data visualization and interpretation. Urine metabolite concentrations previously identified as associated with sepsis in children (e.g., 3-hydroxybutyrate, carnitine, and creatinine) were higher in the patient with fatal MRSA pneumonia compared with those of patients with influenza pneumonia and healthy controls. The concentrations of additional metabolites-acetone, acetoacetate, choline, fumarate, glucose, and 3-aminoisobutyrate-were more than 25-fold higher in the patient with MRSA pneumonia than those of patients with influenza pneumonia and healthy controls. These metabolic changes in the urine preceded the clinical severe sepsis phenotype, suggesting that detection of the extent of metabolic disruption can aid in the early identification of a sepsis phenotype in advance of the clinical diagnosis. These data also support the utility of metabolomics for the development of clinical assays to identify patients with pediatric pneumonia at high risk for deterioration.

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Staphylococcus aureus specific lung resident memory CD4⁺ Th1 cells attenuate the severity of influenza virus induced secondary bacterial pneumonia.

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OmicsDI is part of the ELIXIR infrastructure

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Staphylococcus aureus specific lung resident memory CD4+ Th1 cells attenuate the severity of influenza virus induced secondary bacterial pneumonia.

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OmicsDI is part of the ELIXIR infrastructure

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Staphylococcus aureus specific lung resident memory CD4⁺ Th1 cells attenuate the severity of influenza virus induced secondary bacterial pneumonia.