Abstract
Trypanosoma brucei brucei is the causative agent of African animal trypanosomosis, which mainly parasitizes the blood of the host. Lipophosphoglycan (LPG), a polymer anchored to the surface of the parasites, activates the host immune response. In this study, we revealed that T. brucei LPG stimulated neutrophils to form neutrophil extracellular traps (NETs) and release the reactive oxygen species (ROS). We further analyzed the involvement of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) and explored the activation of signaling pathway enzymes in response to LPG stimulation. During the stimulation of neutrophils by LPG, the blockade using anti-TLR2 and anti-TLR4 antibodies reduced the phosphorylation of c-Jun N-terminal kinase (JNK), the release of DNA from the NETs, and the burst of ROS. Moreover, the addition of JNK inhibitor and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor exhibited similar effects. Our data suggest that T. brucei LPG activates the phosphorylation of JNK through TLR2 and TLR4 recognition, which causes the formation of NETs and the burst of ROS.
Highlights
Trypanosoma brucei brucei, a subspecies of the genus T. brucei, infects a variety of animals in Africa and causes widespread epidemics of African animal trypanosomosis
The liquid chromatography-mass spectrometry (LC-MS) detection of the mass-to-charge ratio (m/z) peak plots showed that we extracted a polymer with a spacing of 229 between the four main peaks (457, 686, 915, and 1,144), indicating the presence of a structural unit with an m/z ratio of 229 in the T. brucei LPG structure (Figure 1B)
Target bands were detected with the sizes of approximately 55, 42, and 35 kDa, respectively, which corresponded with those mentioned in the manual for the anti-LPG monoclonal antibody (Figure 1C)
Summary
Trypanosoma brucei brucei, a subspecies of the genus T. brucei, infects a variety of animals in Africa and causes widespread epidemics of African animal trypanosomosis ( known as trypanosomiasis or Nagana; Guerrini and Bouyer, 2007; Latif et al, 2019; Odeniran et al, 2020). African animal trypanosomiasis is transmitted by tsetse flies into the hosts during blood-sucking and the infected animals suffer from wasting, anemia, neurological symptoms, and even death (Osaer et al, 1999; Diarra et al, 2019) Other pathogens of this genus can Trypanosomal LPG Induces NETs and ROS Burst cause sleeping sickness in humans (Kennedy, 2013; Echodu et al, 2015; Buscher et al, 2017); Trypanosoma-related diseases cause serious disturbances to agricultural production and people’s lives in Africa. Trypanosoma brucei displays a variety of immunogenic substances on its body surface such as variant surface glycoproteins (VSG) and lipophosphoglycan (LPG; Turco, 1992; Urakawa et al, 1997) The former stimulates the hosts to produce specific antibodies against trypanosomes; trypanosomes can evade host-specific immune responses by periodically altering VSG (Manna et al, 2014). Like Leishmania protozoa, trypanosomes display LPG on their surfaces (Hublart et al, 1988; Singh et al, 1994)
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