The ability of Interleukin–10 to negate haemozoin-related pro-inflammatory effects has the potential to restore impaired macrophage function associated with malaria infection

Malaria Journal

Research

Wilson Mandala¹  Terrie E. Taylor²  Karl B. Seydel²  Tam C. Tran³  David G. Russell³  Tonney Nyirenda⁴  Dumizulu Tembo⁵  Visopo Harawa⁵  Malcolm E. Molyneux⁶  Louise Afran⁷ 

[1] Acadamey of Medical Sciences, Malawi University of Science and Technology, Blantyre, Malawi;Blantyre Malaria Project, Blantyre, Malawi;Michigan State University, Michigan, USA;Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA;Kamuzu University of Health Sciences, Blantyre, Malawi;Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi;Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi;Liverpool School of Tropical Medicine, Liverpool, UK;University of Liverpool, Liverpool, UK;Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi;Liverpool School of Tropical Medicine, Liverpool, UK;University of Liverpool, Liverpool, UK;Kamuzu University of Health Sciences, Blantyre, Malawi;

关键词: Malaria;    Cytokines;    Macrophages;    Hemozoin;   

DOI  :  10.1186/s12936-023-04539-w

 received in 2022-10-26, accepted in 2023-03-21,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAlthough pro-inflammatory cytokines are involved in the clearance of Plasmodium falciparum during the early stages of the infection, increased levels of these cytokines have been implicated in the pathogenesis of severe malaria. Amongst various parasite-derived inducers of inflammation, the malarial pigment haemozoin (Hz), which accumulates in monocytes, macrophages and other immune cells during infection, has been shown to significantly contribute to dysregulation of the normal inflammatory cascades.MethodsThe direct effect of Hz-loading on cytokine production by monocytes and the indirect effect of Hz on cytokine production by myeloid cells was investigated during acute malaria and convalescence using archived plasma samples from studies investigating P. falciparum malaria pathogenesis in Malawian subjects. Further, the possible inhibitory effect of IL-10 on Hz-loaded cells was examined, and the proportion of cytokine-producing T-cells and monocytes during acute malaria and in convalescence was characterized.ResultsHz contributed towards an increase in the production of inflammatory cytokines, such as Interferon Gamma (IFN-γ), Tumor Necrosis Factor (TNF) and Interleukin 2 (IL-2) by various cells. In contrast, the cytokine IL-10 was observed to have a dose-dependent suppressive effect on the production of TNF among other cytokines. Cerebral malaria (CM) was characterized by impaired monocyte functions, which normalized in convalescence. CM was also characterized by reduced levels of IFN-γ-producing T cell subsets, and reduced expression of immune recognition receptors HLA-DR and CD 86, which also normalized in convalescence. However, CM and other clinical malaria groups were characterized by significantly higher plasma levels of pro-inflammatory cytokines than healthy controls, implicating anti-inflammatory cytokines in balancing the immune response.ConclusionsAcute CM was characterized by elevated plasma levels of pro-inflammatory cytokines and chemokines but lower proportions of cytokine-producing T-cells and monocytes that normalize during convalescence. IL-10 is also shown to have the potential to indirectly prevent excessive inflammation. Cytokine production dysregulated by the accumulation of Hz appears to impair the balance of the immune response to malaria and exacerbates pathology.

【 授权许可】

CC BY   
© The Author(s) 2023

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