Biochemical and Biophysical Research Communications, Vol.506, No.1, 20-26, 2018
The circulating immunoglobulins negatively impact on the parasite clearance in the liver of Leishmania donovani-infected mice via dampening ROS activity
Visceral leishmaniasis, the most severe form of leishmaniasis, is caused by Leishmania donovani and L infantum. Immunity to Leishmania infection has been shown to depend on the development of Thl cells; however, the roles of B cells and antibodies during infection remain unclear. In the present study, we showed that AID and mu s double-deficient mice (DKO), which have B cells but not circulating immunoglobulins (clgs), became resistant to L. donovani infection, whereas us or AID single-deficient mice did not. This resistance in DKO mice occurred in the liver from an early stage of the infection. The depletion of IFN-gamma did not affect the rapid reduction of parasite burden, whereas NADPH oxidases was up-regulated in the livers of infected DKO mice. The inhibition of the reactive oxygen species pathway in vivo by apocynin, a NADPH oxidase inhibitor, resulted in a significant increase in the parasite burden in DKO mice. These results indicate that a circulating Ig deficiency induces a protective response against L donovani infection by elevating IFN-gamma-independent NADPH oxidase activity, and also that clgs play a regulatory role in controlling L donovani infection in mice. (C) 2018 Elsevier Inc. All rights reserved.