Cross reactive molecules of human lymphatic filaria Brugia malayi inhibit Leishmania donovani infection in hamsters.
Coinfections are common in natural populations and the outcome of their interactions depends on the immune responses of the host elicited by the parasites. Earlier we showed that immunization with BmAFII (Sephadex G-200 eluted) fraction of human lymphatic filaria Brugia malayi inhibited progression of Leishmania donovani infection in golden hamsters. In the present study we identified cross reactive molecules of B. malayi, and investigated their effect on L. donovani infection and associated immune responses in the host. The sequence alignment and sharing of linear T- and B-cell epitopes in protein molecules of B. malayi and L. donovani counterparts were studied in silico. Hamsters were immunized with robustly cross reactive SDS-PAGE resolved fractions F6 (54.2-67.8kDa) and F9 (41.3-45.0kDa) of B. malayi and subsequently inoculated with amastigotes of L. donovani intracardially. F6 inhibited (∼72%) L. donovani infection and upregulated Th1 cytokine expression, lymphoproliferation, IgG2, IgG2/3 levels and NO production, and downregulated Th2 cytokine expression. Sequences in HSP60 and EF-2 of F6 and L. donovani counterparts were conserved and B- and T-cell epitopes in the proteins shared antigenic regions. In conclusion, leishmania-cross reactive molecules of filarial parasite considerably inhibited leishmanial infection via Th1-mediated immune responses and NO production. Common B- and T-cell epitope regions in HSP60 and EF-2 of the parasites might have contributed to the inhibitory effect on the L. donovani infection. Thus, leishmania-cross reactive filarial parasite molecules may help in designing prophylactic(s) against L. donovani.
Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Lucknow 226031, India.
Richa
R
Verma
Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Lucknow 226031, India.
Sujith K
SK
Joseph
Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Lucknow 226031, India.
Vikas
V
Kushwaha
Molecular and Structural Biology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Vistar, Lucknow 226 031, India.
Vikash
V
Kumar
Molecular and Structural Biology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Vistar, Lucknow 226 031, India.
M I
MI
Siddiqi
Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Lucknow 226031, India.
Preeti
P
Vishwakarma
Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Lucknow 226031, India.
Rahul
R
Shivahare
Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Lucknow 226031, India.
Suman
S
Gupta
Division of Parasitology, CSIR-Central Drug Research Institute, New Campus, BS 10/1, Sector 10, Jankipuram Extension, Lucknow 226031, India.
P K
PK
Murthy
D000818:Animals; D017178:Brugia malayi / Q000276:immunology*; D006224:Cricetinae; D016207:Cytokines / Q000097:blood; D018984:Epitopes, T-Lymphocyte; D006801:Humans; D007114:Immunization; D007893:Leishmania donovani / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D008647:Mesocricetus
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte
Brugia malayi; Cross reactive molecules; In silico; Leishmania donovani; T-/B-cell epitopes; Th1 and Th2 responses