Leishmania donovani affects antigen presentation of macrophage by disrupting lipid rafts.
Leishmania donovani-infected splenic macrophages and P388D1 (P388D1(I)) failed to activate T cells in response to low dose of exogenous peptide. The membrane fluidity of P388D1(I) was greater than that of the normal counterpart P388D1(N), but could be reduced either by exposing the cell below phase transition point or by loading cholesterol into membrane (L-P388D1(I)), and this was associated with enhanced Ag-presenting ability of P388D1(I). Presentation of endogenous leishmanial Ag, kinetoplastid membrane protein-11, was also defective, but could be corrected by loading cholesterol into membrane. Because membrane rafts are important for Ag presentation at a low peptide dose, raft architecture of P388D1(I) was studied using raft (CD48 and cholera toxin-B) and non-raft (CD71) markers in terms of their colocalization with I-A(d). Binding of anti-CD48 mAb and cholera toxin B subunit decreased significantly in P388D1(I), and consequently, colocalization with I-A(d) was not seen, but this could be restored in L-P388D1(I). Conversely, colocalization between I-A(d) and CD71 remained unaffected regardless of the presence or the absence of intracellular parasites. P388D1(N) and L-P388D1(I), but not P388D1(I), formed peptide-dependent synapse with T cells quite efficiently and this was found to be corroborated with both intracellular Ca2+ mobilization in T cells and IL-2 production. This indicated that intracellular parasites disrupt the membrane rafts, possibly by increasing the membrane fluidity, which could be corrected by making the membrane rigid. This may be a strategy that intracellular L. donovani adopts to evade host immune system.
Chakraborty
Debabani
D
Department of Immunology, Indian Institute of Chemical Biology, Kolkata, India.
Banerjee
Subha
S
Sen
Abhik
A
Banerjee
Kalyan K
KK
Das
Pradip
P
Roy
Syamal
S
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology; D000953:Antigens, Protozoan / Q000378:metabolism; D000071178:CD48 Antigen; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007893:Leishmania donovani / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D008560:Membrane Fluidity; D021962:Membrane Microdomains / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000953:Antigens, Protozoan; D000071178:CD48 Antigen; C000604066:Cd48 protein, mouse; D000949:Histocompatibility Antigens Class II; D002772:Cholera Toxin; D002784:Cholesterol; D002118:Calcium