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TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis |
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| Authors: | Michael G Drage Amy G Hise Roy L Silverstein W Henry Boom Clifford V Harding |
| Institution: | a Department of Pathology, Case Western Reserve University School of Medicine/University Hospitals Case Medical Center, Wolstein 6534, 10900 Euclid Ave, Cleveland, OH 44106, USA b Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA c Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, and Program in Cell Biology, Case Western Reserve University, Cleveland, OH 44106, USA d Department of Infectious Diseases and Immunology, University of Massachusetts School of Medicine, Worcester, MA 01655, USA e Division of Infectious Diseases and Tuberculosis Research Unit, Case Western Reserve University/University Hospitals Case Medical Center, Cleveland, OH 44106, USA |
| Abstract: | Mycobacterium tuberculosis (Mtb) signals through Toll-like receptor 2 (TLR2) to regulate antigen presenting cells (APCs). Mtb lipoproteins, including LpqH, LprA, LprG and PhoS1, are TLR2 agonists, but their co-receptor requirements are unknown. We studied Mtb lipoprotein-induced responses in TLR2−/−, TLR1−/−, TLR6−/−, CD14−/− and CD36−/− macrophages. Responses to LprA, LprG, LpqH and PhoS1 were completely dependent on TLR2. LprG, LpqH, and PhoS1 were dependent on TLR1, but LprA did not require TLR1. None of the lipoproteins required TLR6, although a redundant contribution by TLR6 cannot be excluded. CD14 contributed to detection of LprA, LprG and LpqH, whereas CD36 contributed only to detection of LprA. Studies of lung APC subsets revealed lower TLR2 expression by CD11bhigh/CD11clow lung macrophages than CD11blow/CD11chigh alveolar macrophages, which correlated with hyporesponsiveness of lung macrophages to LpqH. Thus, lung APC subsets differ in TLR expression, which may determine differences in responses to Mtb. |
| Keywords: | Toll-like receptor 2 Lipoprotein Mycobacterium tuberculosis CD14 CD36 Antigen presenting cell |
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