title: Mycobacterium tuberculosis Strains Are Differentially Recognized by TLRs with an Impact on the Immune Response.
abstract: Tuberculosis associates with a wide spectrum of disease outcomes. The Beijing (Bj) lineage of Mycobacterium tuberculosis (Mtb) is suggested to be more virulent than other Mtb lineages and prone to elicit non-protective immune responses. However, highly heterogeneous immune responses were reported upon infection of innate immune cells with Bj strains or stimulation with their glycolipids. Using both in vitro and in vivo mouse models of infection, we here report that the molecular mechanism for this heterogeneity may be related to distinct TLR activations. Among this Mtb lineage, we found strains that preferentially activate TLR2, and others that also activate TLR4. Recognition of Mtb strains by TLR4 resulted in a distinct cytokine profile in vitro and in vivo, with specific production of type I IFN. We also uncover a novel protective role for TLR4 activation in vivo. Thus, our findings contribute to the knowledge of the molecular basis underlying how host innate immune cells handle different Mtb strains, in particular the intricate host-pathogen interaction with strains of the Mtb Bj lineage.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal ; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Jenny
authors.initials: J
authors.lastname: Carmona
authors.forename: Andrea
authors.initials: A
authors.lastname: Cruz
authors.forename: Lucia
authors.initials: L
authors.lastname: Moreira-Teixeira
authors.forename: Carole
authors.initials: C
authors.lastname: Sousa
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sousa
authors.forename: Nuno S
authors.initials: NS
authors.lastname: Osorio
authors.forename: Ana L
authors.initials: AL
authors.lastname: Saraiva
authors.forename: Stefan
authors.initials: S
authors.lastname: Svenson
authors.forename: Gunilla
authors.initials: G
authors.lastname: Kallenius
authors.forename: Jorge
authors.initials: J
authors.lastname: Pedrosa
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodrigues
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Castro
authors.forename: Margarida
authors.initials: M
authors.lastname: Saraiva
mesh_terms: D000818:Animals; D005260:Female; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D013045:Species Specificity; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4