TREM-1 modulation produces positive outcome on the histopathology and cytokines release profile of Plasmodium berghei-infected mice
Triggering receptor expressed on myeloid cells 1 (TREM-1) is a potential molecular therapeutic target for various inflammatory diseases. Despite that, the role of TREM-1 during malaria pathogenesis remains obscure with present literature suggesting a link between TREM-1 with severe malaria development. Therefore, this study aims to investigate the role of TREM-1 and TREM-1 related drugs during severe malaria infection in Plasmodium berghei-infected mice model. Our findings revealed that TREM-1 concentration was significantly increased throughout the infection periods and TREM-1 was positively correlated with malaria parasitemia development. This suggests a positive involvement of TREM-1 in severe malaria development. Meanwhile, blocking of TREM-1 activation using rmTREM-1/Fc and TREM-1 clearance by mTREM-1/Ab had significantly reduced malaria parasitemia and suppressed the production of pro- inflammatory cytokines (TNF-α, IL-6 and IFN-γ) and anti-inflammatory cytokine (IL-10). Furthermore, histopathological analysis of TREM-1 related drug treatments, in particular rmTREM-1/Fc showed significant improvements in the histological conditions of major organs (kidneys, spleen, lungs, liver and brain) of Plasmodium berghei-infected mice. This study showed that modulation of TREM-1 released during malaria infection produces a positive outcome on malaria infection through inhibition of pro-inflammatory cytokines secretion and alleviation of histopathological conditions of affected organs. Nevertheless, further investigation on its optimal dosage and dose dependant study should be carried out to maximise its full potential as immunomodulatory or as an adjuvant in line with current antimalarial agents.
KeywordsTREM-1 Experimental malaria infection Cytokines Histopathology TREM-1 modulation
We would like to acknowledge Universiti Putra Malaysia, Malaysia and Ministry of Education, Malaysia under Fundamental Research Grant Scheme (FRGS) (04-11-08-629FR) for providing financial and infrastructure support for the conduction of the research study.
AAMY conducted the experiments and analyzed the data in this study. CVK analyzed the data, wrote and revised the manuscript. RB conceptualized the idea and experimental design in this study. RB, WOA, CPP, NN, ZOI and RAM provide technical supports in the experiments and revised the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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