Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis.
Macrophages play an essential role in the early immune response to Mycobacterium tuberculosis and are the cell type preferentially infected in vivo. Primary macrophages and macrophage-like cell lines are commonly used as infection models, although the physiological relevance of cell lines, particularly for host-pathogen interaction studies, is debatable. Here we use high-throughput RNA-sequencing to analyse transcriptome dynamics of two macrophage models in response to M. tuberculosis infection. Specifically, we study the early response of bone marrow-derived mouse macrophages and cell line J774 to infection with live and γ-irradiated (killed) M. tuberculosis. We show that infection with live bacilli specifically alters the expression of host genes such as Rsad2, Ifit1/2/3 and Rig-I, whose potential roles in resistance to M. tuberculosis infection have not yet been investigated. In addition, the response of primary macrophages is faster and more intense than that of J774 cells in terms of number of differentially expressed genes and magnitude of induction/repression. Our results point to potentially novel processes leading to immune containment early during M. tuberculosis infection, and support the idea that important differences exist between primary macrophages and cell lines, which should be taken into account when choosing a macrophage model to study host-pathogen interactions.
Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, UK.
Nuria
N
Andreu
Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, UK.
Jody
J
Phelan
Genome Institute of Singapore, A*STAR, Singapore.
Paola F
PF
de Sessions
TB Centre and Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, UK.
Jacqueline M
JM
Cliff
Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, UK.|Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
Taane G
TG
Clark
Pathogen Molecular Biology Department, London School of Hygiene and Tropical Medicine, London, UK.|Genome Institute of Singapore, A*STAR, Singapore.
Martin L
ML
Hibberd
D000818:Animals; D002478:Cells, Cultured; D005720:Gamma Rays; D020869:Gene Expression Profiling; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000473:pathology* / Q000528:radiation effects; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000502:physiology* / Q000528:radiation effects; D014158:Transcription, Genetic / Q000528:radiation effects; D059467:Transcriptome / Q000235:genetics; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*