title: Mycobacterium tuberculosis inhibits neutrophil apoptosis, leading to delayed activation of naive CD4 T cells.
abstract: Mycobacterium tuberculosis promotes its replication by inhibiting the apoptosis of infected macrophages. A proapoptotic M. tuberculosis mutant lacking nuoG, a subunit of the type I NADH dehydrogenase complex, exhibits attenuated growth in vivo, indicating that this virulence mechanism is essential. We show that M. tuberculosis also suppresses neutrophil apoptosis. Compared to wild-type, the nuoG mutant spread to a larger number of lung phagocytic cells. Consistent with the shorter lifespan of infected neutrophils, infection with the nuoG mutant resulted in fewer bacteria per infected neutrophil, accelerated bacterial acquisition by dendritic cells, earlier trafficking of these dendritic cells to lymph nodes, and faster CD4 T cell priming. Neutrophil depletion abrogated accelerated CD4 T cell priming by the nuoG mutant, suggesting that inhibiting neutrophil apoptosis delays adaptive immunity in tuberculosis. Thus, pathogen modulation of apoptosis is beneficial at multiple levels, and enhancing phagocyte apoptosis promotes CD4 as well as CD8 T cell responses.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Blomgran
authors.forename: Ludovic
authors.initials: L
authors.lastname: Desvignes
authors.forename: Volker
authors.initials: V
authors.lastname: Briken
authors.forename: Joel D
authors.initials: JD
authors.lastname: Ernst
mesh_terms: D017209:Apoptosis; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000382:microbiology; D017353:Gene Deletion; D057131:Immune Evasion; D008198:Lymph Nodes / Q000382:microbiology; D008213:Lymphocyte Activation; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity*; D009504:Neutrophils / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors