Mycobacterium tuberculosis infection of dendritic cells leads to partially caspase-1/11-independent IL-1β and IL-18 secretion but not to pyroptosis

• Published in: PloS one Vol. 7; no. 7; p. e40722
• Main Authors: Abdalla, Hana, Srinivasan, Lalitha, Shah, Swati, Mayer-Barber, Katrin D, Sher, Alan, Sutterwala, Fayyaz S, Briken, Volker
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.07.2012; Public Library of Science (PLoS)
• Subjects: Animals; Antigens; Apoptosis; Apoptosis - immunology; Apoptosis Regulatory Proteins; Bacillus anthracis; Biology; Bone marrow; Candida albicans; CARD Signaling Adaptor Proteins; Carrier Proteins - metabolism; Caspase; Caspase 1 - metabolism; Caspase-1; Caspases - metabolism; Cell death; Clonal deletion; Cytokines; Cytoskeletal Proteins - metabolism; Deletion mutant; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Genes; Homeodomain Proteins - metabolism; Immune response; Immune system; Infections; Infectious diseases; Inflammasomes; Inflammasomes - immunology; Inflammasomes - metabolism; Innate immunity; Interleukin 18; Interleukin-18 - secretion; Interleukin-1beta - secretion; Laboratories; Medicine; Mice; Mice, Knockout; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Necrosis - immunology; Neurotoxicity; NLR Family, Pyrin Domain-Containing 3 Protein; NOD2 protein; Parasitic diseases; Pathogens; Proteins; Pyroptosis; Regulation; Tuberculosis; Tuberculosis - immunology; Tuberculosis - metabolism; United States > US; Maryland; Iowa City Iowa
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0040722

Interleukin-1β (IL-1β) is important for host resistance against Mycobacterium tuberculosis (Mtb) infections. The response of the dendritic cell inflammasome during Mtb infections has not been investigated in detail. Here we show that Mtb infection of bone marrow-derived dendritic cells (BMDCs) induces IL-1β secretion and that this induction is dependent upon the presence of functional ASC and NLRP3 but not NLRC4 or NOD2. The analysis of cell death induction in BMDCs derived from these knock-out mice revealed the important induction of host cell apoptosis but not necrosis, pyroptosis or pyronecrosis. Furthermore, NLRP3 inflammasome activation and apoptosis induction were both reduced in BMDCs infected with the esxA deletion mutant of Mtb demonstrating the importance of a functional ESX-1 secretion system. Surprisingly, caspase-1/11-deficient BMDCs still secreted residual levels of IL-1βand IL-18 upon Mtb infection which was abolished in cells infected with the esxA Mtb mutant. Altogether we demonstrate the partially caspase-1/11-independent, but NLRP3- and ASC-dependent IL-1β secretion in Mtb-infected BMDCs. These findings point towards a potential role of DCs in the host innate immune response to mycobacterial infections via their capacity to induce IL-1β and IL-18 secretion.