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10.1371/journal.pntd.0004710 http://scihub22266oqcxt.onion/10.1371/journal.pntd.0004710 C4877013!4877013 !27214205     free     free     free Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\27214205 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       PLoS+Negl+Trop+Dis 2016 ; 10 (5 ): e0004710 Nephropedia Template TP {{tp|p=27214205 |t=2016. Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy |pdf=|usr=}}{{27214205 }} gab.com Text Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy JO: PLoS Negl Trop Dis http://www.kidney.de/pget.php?&tw=1&pmid=27214205 #FOAvip BACKGROUND: Previously we reported that Kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. Splenic macrophages (M?) of Leishmania donovani (LD) infected mice show decrease in membrane cholesterol, while LD infected macrophages (I-M?) show defective T cell stimulating ability that could be corrected by liposomal delivery of cholesterol. T helper cells recognize peptide antigen in the context of class II MHC molecule. It is known that the conformation of a large number of membrane proteins is dependent on membrane cholesterol. In this investigation we tried to understand the influence of decreased membrane cholesterol in I-M? on the conformation of MHC-II protein and peptide-MHC-II stability, and its bearing on the antigen specific T-cell activation. METHODOLOGY/PRINCIPAL FINDINGS: M? of CBA/j mice were infected with Leishmania donovani (I-M?). Two different anti-A? mAbs were used to monitor the status of MHC-II protein under parasitized condition. One of them (11.5-2) was conformation specific, whereas the other one (10.2.16) was not. Under parasitized condition, the binding of 11.5-2 decreased significantly with respect to the normal counterpart, whereas that of 10.2.16 remained unaltered. The binding of 11.5-2 was restored to normal upon liposomal delivery of cholesterol in I-M?. By molecular dynamics (MD) simulation studies we found that there was considerable conformational fluctuation in the transmembrane domain of the MHC-II protein in the presence of membrane cholesterol than in its absence, which possibly influenced the distal peptide binding groove. This was evident from the faster dissociation of the cognate peptide from peptide-MHC complex under parasitized condition, which could be corrected by liposomal delivery of cholesterol in I-M?. CONCLUSION: The decrease in membrane cholesterol in I-M? may lead to altered conformation of MHC II, and this may contribute to a faster dissociation of the peptide. Furthermore, liposomal delivery of cholesterol in I-M? restored its normal antigen presenting function. This observation brings strength to our previous observation on host directed therapeutic application of liposomal cholesterol in experimental visceral leishmaniasis. Twit Text FOAVip Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy ????PLoS Negl Trop Dis http://www.kidney.de/pget.php?&tw=1&pmid=27214205 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27214205 #FOAvip English Wikipedia <ref>{{Cite pmid|27214205 }}</ref> Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishmania donovani Infected Macrophages: Implication in Therapy #MMPMID27214205 Roy K ; Mandloi S ; Chakrabarti S ; Roy S PLoS Negl Trop Dis 2016[May]; 10 (5 ): e0004710 PMID27214205 show ga BACKGROUND: Previously we reported that Kala-azar patients show progressive decrease in serum cholesterol as a function of splenic parasite burden. Splenic macrophages (M?) of Leishmania donovani (LD) infected mice show decrease in membrane cholesterol, while LD infected macrophages (I-M?) show defective T cell stimulating ability that could be corrected by liposomal delivery of cholesterol. T helper cells recognize peptide antigen in the context of class II MHC molecule. It is known that the conformation of a large number of membrane proteins is dependent on membrane cholesterol. In this investigation we tried to understand the influence of decreased membrane cholesterol in I-M? on the conformation of MHC-II protein and peptide-MHC-II stability, and its bearing on the antigen specific T-cell activation. METHODOLOGY/PRINCIPAL FINDINGS: M? of CBA/j mice were infected with Leishmania donovani (I-M?). Two different anti-A? mAbs were used to monitor the status of MHC-II protein under parasitized condition. One of them (11.5-2) was conformation specific, whereas the other one (10.2.16) was not. Under parasitized condition, the binding of 11.5-2 decreased significantly with respect to the normal counterpart, whereas that of 10.2.16 remained unaltered. The binding of 11.5-2 was restored to normal upon liposomal delivery of cholesterol in I-M?. By molecular dynamics (MD) simulation studies we found that there was considerable conformational fluctuation in the transmembrane domain of the MHC-II protein in the presence of membrane cholesterol than in its absence, which possibly influenced the distal peptide binding groove. This was evident from the faster dissociation of the cognate peptide from peptide-MHC complex under parasitized condition, which could be corrected by liposomal delivery of cholesterol in I-M?. CONCLUSION: The decrease in membrane cholesterol in I-M? may lead to altered conformation of MHC II, and this may contribute to a faster dissociation of the peptide. Furthermore, liposomal delivery of cholesterol in I-M? restored its normal antigen presenting function. This observation brings strength to our previous observation on host directed therapeutic application of liposomal cholesterol in experimental visceral leishmaniasis. |Animals [MESH] |Antigen Presentation/immunology [MESH] |Cell Membrane/*chemistry [MESH] |Cholesterol/administration & dosage/*metabolism [MESH] |Histocompatibility Antigens Class II/*chemistry/immunology/metabolism [MESH] |Leishmania donovani/metabolism [MESH] |Leishmaniasis, Visceral/immunology/parasitology/*therapy [MESH] |Liposomes [MESH] |Macrophages/chemistry/*immunology/*parasitology [MESH] |Membrane Lipids/metabolism [MESH] |Membrane Proteins/metabolism [MESH] |Mice [MESH] |Mice, Inbred BALB C [MESH] |Mice, Inbred CBA [MESH] |Molecular Dynamics Simulation [MESH] |Protein Binding/immunology [MESH]Cholesterol Corrects Altered Conformation of MHC-II Protein in Leishma(epmc).pdf DeepDyve Pubget Overpricing