Mycobacterium tuberculosis Strains Are Differentially Recognized by TLRs with an Impact on the Immune Response |
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| Authors: | Jenny Carmona Andrea Cruz Lucia Moreira-Teixeira Carole Sousa Jeremy Sousa Nuno S Osorio Ana L Saraiva Stefan Svenson Gunilla Kallenius Jorge Pedrosa Fernando Rodrigues Antonio G Castro Margarida Saraiva |
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| Institution: | 1. Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.; 2. ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal.; 3. Escola Universitária Vasco da Gama (EUVG), Coimbra, Portugal.; 4. Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden.; Emory University School of Medicine, United States of America, |
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| 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. |
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