Dr. Roland Lang - Macrophages dealing with intracellular bacteria: from mycobacterial glycolipids to control of Coxiella by itaconate - IPBS-Toulouse, Seminar Room

Roland Lang Institute of Clinical Microbiology, Immunology and Hygiene, University Hospital Erlangen, Germany Macrophages are specialized taking up, sensing and eliminating bacterial pathogens. Specialized intracellular bacteria use different strategies to establish a niche within macrophages, to persist for long time and to reactivate replication at some time in some individuals. It is a fascinating question which host and bacterial factors determine whether such infections are successfully eliminated and resolved, or lead to persistence and chronic disease. My lab has an interest in answering these questions particularly from the host perspective for infections with mycobacteria and with Coxiella burnetii. The mycobacterial cord factor trehalose-6,6’-dimycolate plays an important role in tuberculosis as it elicits several key aspects of the host response. I will present our recent work on reciprocal regulation of the cord factor receptor Mincle by the cytokines TNF and IL-4 in mouse infection and vaccination models. In the second part of the talk, I will focus on the identification of ACOD1-dependent generation of the immune-metabolite itaconate as an essential early defense mechanism against the Q fever-causing Coxiella burnetii. Open questions on the anti-microbial and immunoregulatory effects and mechanisms of itaconate, as well as its therapeutic potential will be discussed. Selected references

• Schick, J., M. Altunay, M. Lacorcia, N. Marschner, S. Westermann, J. Schluckebier, C. Schubart, B. Bodendorfer, D. Christensen, C. Alexander, S. Wirtz, D. Voehringer, C. P. da Costa, and R. Lang. 2023. IL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity. Elife 12: https://doi.org/10.7554/eLife.72923
• Kohl, L., M. Siddique, B. Bodendorfer, R. Berger, A. Preikschat, C. Daniel, M. Olke, E. Liebler-Tenorio, J. Schulze-Luehrmann, M. Mauermeir, K. T. Yang, I. Hayek, M. Szperlinski, J. Andrack, U. Schleicher, A. Bozec, G. Kronke, P. J. Murray, S. Wirtz, M. Yamamoto, V. Schatz, J. Jantsch, P. Oefner, D. Degrandi, K. Pfeffer, K. Mertens-Scholz, S. Rauber, C. Bogdan, K. Dettmer, A. Luhrmann, and R. Lang. 2023. Macrophages inhibit Coxiella burnetii by the ACOD1-itaconate pathway for containment of Q fever. EMBO Mol Med 15: e15931
• Schick, J., J. Schafer, C. Alexander, S. Dichtl, P. J. Murray, D. Christensen, U. Sorg, K. Pfeffer, U. Schleicher, and R. Lang. 2020. Cutting Edge: TNF Is Essential for Mycobacteria-Induced MINCLE Expression, Macrophage Activation, and Th17 Adjuvanticity. J Immunol 205: 323-328
• Kohl, L., I. Hayek, C. Daniel, J. Schulze-Luhrmann, B. Bodendorfer, A. Luhrmann, and R. Lang. 2019. MyD88 Is Required for Efficient Control of Coxiella burnetii Infection and Dissemination. Front Immunol 10: 165