Differential Microbicidal Effects of Human Histone Proteins H2A and H2B on
Leishmania
Promastigotes and Amastigotes
Publication
, Journal Article
Wang, Y; Chen, Y; Xin, L; Beverley, SM; Carlsen, ED; Popov, V; Chang, K-P; Wang, M; Soong, L
Published in: Infection and Immunity
Recent studies have shown that histone proteins can act as antimicrobial peptides in host defense against extracellular bacteria, fungi, and
promastigotes. In this study, we used human recombinant histone proteins to further study their leishmaniacidal effects and the underlying mechanisms. We found that the histones H2A and H2B (but not H1
) could directly and efficiently kill promastigotes of
,
,
, and
in a treatment dose-dependent manner. Scanning electron microscopy revealed surface disruption of histone-treated promastigotes. More importantly, the preexposure of promastigotes to histone proteins markedly decreased the infectivity of promastigotes to murine macrophages (Mφs)
. However, axenic and lesion-derived amastigotes of
and
were relatively resistant to histone treatment, which correlated with the low levels of intracellular H2A in treated amastigotes. To understand the mechanisms underlying these differential responses, we investigated the role of promastigote surface molecules in histone-mediated killing. Compared with the corresponding controls, transgenic
promastigotes expressing lower levels of surface gp63 proteins were more susceptible to histone H2A, while
and
promastigotes with targeted deletion of the lipophosphoglycan 2 (
) gene (but not the
gene) were more resistant to histone H2A. We discuss the influence of promastigote major surface molecules in the leishmaniacidal effect of histone proteins. This study provides new information on host innate immunity to different developmental stages of
parasites.
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