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Failure to induce IFN-? production during Staphylococcus aureus infection contributes to pathogenicity.

ABSTRACT: The importance of type I IFNs in the host response to viral infection is well established; however, their role in bacterial infection is not fully understood. Several bacteria (both Gram-positive and -negative) have been shown to induce IFN-? production in myeloid cells, but this IFN-? is not always beneficial to the host. We examined whether Staphylococcus aureus induces IFN-? from myeloid phagocytes, and if so, whether it is helpful or harmful to the host to do so. We found that S. aureus poorly induces IFN-? production compared with other bacteria. S. aureus is highly resistant to degradation in the phagosome because it is resistant to lysozyme. Using a mutant that is more sensitive to lysozyme, we show that phagosomal degradation and release of intracellular ligands is essential for induction of IFN-? and inflammatory chemokines downstream of IFN-?. Further, we found that adding exogenous IFN-? during S. aureus infection (in vitro and in vivo) was protective. Together, the data demonstrate that failure to induce IFN-? production during S. aureus infection contributes to pathogenicity.

SUBMITTER: Kaplan A

PROVIDER: S-EPMC3478442 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Failure to induce IFN-β production during Staphylococcus aureus infection contributes to pathogenicity.

Kaplan Amber A Ma Jun J Kyme Pierre P Wolf Andrea J AJ Becker Courtney A CA Tseng Ching Wen CW Liu George Y GY Underhill David M DM

Journal of immunology (Baltimore, Md. : 1950) 20120924 9

The importance of type I IFNs in the host response to viral infection is well established; however, their role in bacterial infection is not fully understood. Several bacteria (both Gram-positive and -negative) have been shown to induce IFN-β production in myeloid cells, but this IFN-β is not always beneficial to the host. We examined whether Staphylococcus aureus induces IFN-β from myeloid phagocytes, and if so, whether it is helpful or harmful to the host to do so. We found that S. aureus poor ...[more]

PMID: 23008447

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Project description:Laboratory models have been invaluable for the field of microbiology for over 100?years and have provided key insights into core aspects of bacterial physiology such as regulation and metabolism. However, it is important to identify the extent to which these models recapitulate bacterial physiology within a human infection environment. Here, we performed transcriptomics (RNA-seq), focusing on the physiology of the prominent pathogen Staphylococcus aureus in situ in human cystic fibrosis (CF) infection. Through principal-component and hierarchal clustering analyses, we found remarkable conservation in S. aureus gene expression in the CF lung despite differences in the patient clinic, clinical status, age, and therapeutic regimen. We used a machine learning approach to identify an S. aureus transcriptomic signature of 32 genes that can reliably distinguish between S. aureus transcriptomes in the CF lung and in vitro The majority of these genes were involved in virulence and metabolism and were used to improve a common CF infection model. Collectively, these results advance our knowledge of S. aureus physiology during human CF lung infection and demonstrate how in vitro models can be improved to better capture bacterial physiology in infection.IMPORTANCE Although bacteria have been studied in infection for over 100?years, the majority of these studies have utilized laboratory and animal models that often have unknown relevance to the human infections they are meant to represent. A primary challenge has been to assess bacterial physiology in the human host. To address this challenge, we performed transcriptomics of S. aureus during human cystic fibrosis (CF) lung infection. Using a machine learning framework, we defined a "human CF lung transcriptome signature" that primarily included genes involved in metabolism and virulence. In addition, we were able to apply our findings to improve an in vitro model of CF infection. Understanding bacterial gene expression within human infection is a critical step toward the development of improved laboratory models and new therapeutics.

Dataset Information

Failure to induce IFN-? production during Staphylococcus aureus infection contributes to pathogenicity.

Publications

Failure to induce IFN-β production during Staphylococcus aureus infection contributes to pathogenicity.

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