Unknown,Transcriptomics,Genomics,Proteomics

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Mouse-Monkey Time-series

ABSTRACT: Viral and bacterial infections of the lower respiratory tract are major causes of mortality and morbidity worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. In the study we examined the response of alveolar macrophages from mice and cynomolgus macaques to two viral (PR8 and Fuj/02 influenza A) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens. Cells were isolated by bronchoalveolar lavage, exposed to pathogen. Cells and supernatants were collected at defined time points to determine changes in gene expression profile and cytokine production respectively. Our analyses identified a core set of genes that were differentially expressed in both species and across all pathogens. The genes upregulated by all infections in both mouse and monkey fell into the interferon response pathway. Interestingly the AM response to Mtb differed markedly between the two species, despite the fact that robust responses were induced in both species. We observed divergent responses to the two influenza viruses in both species such that murine AM responded to Fuj/02 but not PR8 whereas AM from macaques responded to PR8 and not Fuj/02. A similar phenomenon was observed with AM infected with Ft.S4 in that murine AM mounted a transient response, which was rapidly aborted, whereas macaque AM responded vigorously to this pathogen. These studies provide a comprehensive analysis of the response of a key cell type in the pulmonary innate immune system and identify differences and similarities between responses to lethal and self contained infections.

ORGANISM(S): Macaca_fascicularis

SUBMITTER: Alexander Connor

PROVIDER: E-MTAB-427 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Cigarette smoking is the leading cause of the respiratory diseases collectively known as chronic obstructive pulmonary disease (COPD). While the pathogenesis of COPD is complex, there is abundant evidence that alveolar macrophages (AM) play an important role. Based on the concept that COPD is a slow-progressing disorder likely involving multiple mediators released by AM activated by cigarette smoke, the present study focuses on the identification of previously unrecognized genes that may be linked to early events in the molecular pathogenesis of COPD, as opposed to factors associated with the presence of disease. To accomplish this, microarray analysis using Affymetrix microarrays was used to carry out an unbiased survey of the differences in gene expression profiles in the AM of phenotypically normal, ~20 pack-yr smokers compared to healthy non-smokers. Although smoking did not alter the global gene expression pattern of AM, 75 genes were modulated by smoking, with 40 genes up-regulated and 35 down-regulated in the AM of smokers compared to non-smokers. Most of these genes belong to the functional categories of immune/inflammatory response, cell adhesion and extracellular matrix, proteolysis and antiproteolysis, lysosomal function, antioxidant-related, signal transduction and regulation of transcription. Of these 75 genes, 69 have not been previously recognized to be up- or down-regulated in alveolar macrophages in association with smoking or COPD, including genes coding for proteins belonging to all of the above categories, and others belonging to various functional categories or of unknown function. These observations suggest that gene expression responses of alveolar macrophages associated with the stress of cigarette smoking are more complex than previously thought, and offer a variety of new insights into the complex pathogenesis of smoking-induced lung diseases. Experiment Overall Design: 5 non smokers and 5 smokers Experiment Overall Design: Alveolar macrophages were obtained from bronchoalveolar lavage

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Mouse-Monkey Time-series

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