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• W4281986127 abstract "Abstract Mycobacterium ulcerans is the causative agent of the chronic and debilitating neglected tropical disease Buruli ulcer (BU) which mostly affects children. The early detection and treatment of M. ulcerans infections can significantly minimize life-long disability resulting from surgical intervention. However, the disease is characterized by relatively few systemic systems as a result of complex host-pathogen interactions that have yet to be fully characterized, which has limited the development of both diagnostic and therapeutic approaches to treat BU. In this work, we study the interactions of the host immune system with two principle M. ulcerans virulence factors: mycolactone, an amphiphilic macrolide toxin, and lipoarabinomannan (LAM), a cell wall component of most mycobacterial pathogens. We observe that human lipoproteins have a profound effect on the interaction of both mycolactone and LAM with the immune system. Individually, both molecules are pro-inflammatory in the absence of serum and immunosuppressive in the presence of serum. When combined, mycolactone and LAM are immunosuppressive regardless of serum conditions. We also show that Toll-like receptor 2 (TLR2), a macrophage pathogen pattern recognition receptor, is critical for LAM immune stimulation but aids in mycolactone immunosuppression. These findings are a first step towards unraveling mycolactone-mediated immunosuppression during BU disease and may facilitate the development of effective diagnostics and therapeutics in the future. Author Summary Buruli ulcer (BU) is a neglected tropical disease caused by the pathogen Mycobacterium ulcerans . The principal virulence factors associated with it are the macrolide toxin mycolactone and the major cell wall component lipoarabinomannan (LAM). Here, we examine the impact of the amphiphilic biochemistry of mycolactone and LAM on their interaction with the human immune system. We show that both mycolactone and LAM associate with serum lipoproteins, and that this association is critical for the immune evasion seen in early-stage M. ulcerans infections. In the absence of serum, mycolactone is pro-inflammatory. Immunosuppression occurs only in the presence of human serum lipoproteins. In the presence of LAM, mycolactone is immunosuppressive, regardless of serum conditions. Immunosuppression is a hallmark of BU disease, and understanding the mechanisms of this immunosuppression can support the development of effective diagnostic and therapeutic strategies." @default.
• W4281986127 created "2022-06-13" @default.
• W4281986127 creator A5003480770 @default.
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• W4281986127 date "2022-06-06" @default.
• W4281986127 modified "2023-09-27" @default.
• W4281986127 title "Serum lipoproteins and lipoarabinomannan suppress the inflammatory response induced by the mycolactone toxin" @default.
• W4281986127 cites W1856081267 @default.
• W4281986127 cites W1895671845 @default.
• W4281986127 cites W1918758890 @default.
• W4281986127 cites W1969734146 @default.
• W4281986127 cites W1972348350 @default.
• W4281986127 cites W1990844197 @default.
• W4281986127 cites W1993326236 @default.
• W4281986127 cites W1995744610 @default.
• W4281986127 cites W2001802908 @default.
• W4281986127 cites W2006371130 @default.
• W4281986127 cites W2017754180 @default.
• W4281986127 cites W2035462737 @default.
• W4281986127 cites W2039054540 @default.
• W4281986127 cites W2057339612 @default.
• W4281986127 cites W2057353295 @default.
• W4281986127 cites W2058846240 @default.
• W4281986127 cites W2066311301 @default.
• W4281986127 cites W2068290146 @default.
• W4281986127 cites W2070320537 @default.
• W4281986127 cites W2077626956 @default.
• W4281986127 cites W2078840595 @default.
• W4281986127 cites W2086330982 @default.
• W4281986127 cites W2092682849 @default.
• W4281986127 cites W2094555435 @default.
• W4281986127 cites W2098777254 @default.
• W4281986127 cites W2102578857 @default.
• W4281986127 cites W2105159335 @default.
• W4281986127 cites W2106248075 @default.
• W4281986127 cites W2106531384 @default.
• W4281986127 cites W2107323176 @default.
• W4281986127 cites W2116210034 @default.
• W4281986127 cites W2118834179 @default.
• W4281986127 cites W2123888778 @default.
• W4281986127 cites W2124307580 @default.
• W4281986127 cites W2129442719 @default.
• W4281986127 cites W2133240653 @default.
• W4281986127 cites W2139744167 @default.
• W4281986127 cites W2141526752 @default.
• W4281986127 cites W2150059429 @default.
• W4281986127 cites W2151892531 @default.
• W4281986127 cites W2166258374 @default.
• W4281986127 cites W2173406198 @default.
• W4281986127 cites W2271914866 @default.
• W4281986127 cites W2282741333 @default.
• W4281986127 cites W2319276292 @default.
• W4281986127 cites W2319682441 @default.
• W4281986127 cites W2324376717 @default.
• W4281986127 cites W2407167554 @default.
• W4281986127 cites W2528387992 @default.
• W4281986127 cites W2554580112 @default.
• W4281986127 cites W2598239665 @default.
• W4281986127 cites W2604122773 @default.
• W4281986127 cites W2724566643 @default.
• W4281986127 cites W2751159786 @default.
• W4281986127 cites W2765120344 @default.
• W4281986127 cites W2782883240 @default.
• W4281986127 cites W2787658627 @default.
• W4281986127 cites W2792240974 @default.
• W4281986127 cites W2808062199 @default.
• W4281986127 cites W2808728877 @default.
• W4281986127 cites W2883817407 @default.
• W4281986127 cites W2884477134 @default.
• W4281986127 cites W2896505809 @default.
• W4281986127 cites W2902677197 @default.
• W4281986127 cites W2927893242 @default.
• W4281986127 cites W2939772398 @default.
• W4281986127 cites W2943663547 @default.
• W4281986127 cites W2948286924 @default.
• W4281986127 cites W2953022741 @default.
• W4281986127 cites W2964789642 @default.
• W4281986127 cites W2969718750 @default.
• W4281986127 cites W2982145969 @default.
• W4281986127 cites W2998006775 @default.
• W4281986127 cites W3004541069 @default.
• W4281986127 cites W3007316996 @default.
• W4281986127 cites W3011809677 @default.
• W4281986127 cites W3014886878 @default.
• W4281986127 cites W3037909599 @default.
• W4281986127 cites W3096828292 @default.
• W4281986127 cites W3111493690 @default.
• W4281986127 cites W3149036111 @default.
• W4281986127 cites W3163596674 @default.
• W4281986127 cites W3205472923 @default.
• W4281986127 cites W4221137816 @default.
• W4281986127 cites W4233395587 @default.
• W4281986127 cites W4281712756 @default.
• W4281986127 cites W4294216483 @default.
• W4281986127 doi "https://doi.org/10.1101/2022.06.06.494992" @default.

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