title: The hypervirulent Mycobacterium tuberculosis strain HN878 induces a potent TH1 response followed by rapid down-regulation.
abstract: The HN878 strain of Mycobacterium tuberculosis is regarded as "hypervirulent" due to its rapid growth and reduced survival of infected mice when compared with other clinical isolates. This property has been ascribed due to an early increase in type I IFNs and a failure to generate TH1-mediated immunity, induced by a response to an unusual cell wall phenolic glycolipid expressed by the HN878 isolate. We show, however, that although type I IFN does play an inhibitory role, this response was most apparent during the chronic disease stage and was common to all M. tuberculosis strains tested. In addition, we further demonstrate that the HN878 infection was associated with a potent TH1 response, characterized by the emergence of both CD4 and CD8 T cell subsets secreting IFN-gamma. However, where HN878 differed to the other strains tested was a subsequent reduction in TH1 immunity, which was temporally associated with the rapid emergence of a CD4+CD25+FoxP3+CD223+IL-10+ regulatory T cell population. This association may explain the paradoxical initial emergence of a TH1 response in these mice but their relatively short time of survival.
authors.affiliation: Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA. D.Ordway-Rodriguez@colostate.edu
authors.forename: Diane
authors.initials: D
authors.lastname: Ordway
authors.forename: Marcela
authors.initials: M
authors.lastname: Henao-Tamayo
authors.forename: Marisa
authors.initials: M
authors.lastname: Harton
authors.forename: Gopinath
authors.initials: G
authors.lastname: Palanisamy
authors.forename: Jolynn
authors.initials: J
authors.lastname: Troudt
authors.forename: Crystal
authors.initials: C
authors.lastname: Shanley
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Basaraba
authors.forename: Ian M
authors.initials: IM
authors.lastname: Orme
mesh_terms: D000818:Animals; D016516:CD4-CD8 Ratio; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005260:Female; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity*; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D014774:Virulence
chemical_list: D016207:Cytokines; D053633:Receptor, Interferon alpha-beta