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Hemozoin From the Liver Fluke, Opisthorchis felineus, Modulates Dendritic Cell Responses in Bronchial Asthma Patients.

ABSTRACT: Aims: There is a general, inverse relationship between helminth infection and allergic diseases including bronchial asthma (BA). Proteins and other mediators released from parasitic worms exert cogent downmodulation of atopic and other allergic reactivity. We investigated the immune activities of an immortalized murine dendritic cell (mDC) line (JAWSII) and of primary human dendritic cells (hDCs) collected from study participants with and without BA after Opisthorchis felineus hemozoin (OfHz) treatment. Methods and Results: in vitro, expression of lymphocyte-activating factors-T helper 1 (Th1) induction and anti-inflammatory cytokines including tumor necrosis factor alpha (TNF-?), interleukin-1beta (IL-1?), IL-10, and IL-12?-increased significantly in mDCs pulsed with OfHz. In parallel, primary dendritic cells (hDC) from cases clinically diagnosed with BA along with healthy controls were exposed ex vivo to OfHz in combination with lipopolysaccharide (LPS). Whereas no significant change in the cellular maturation markers, CD83, CD86, and CD40, was apparent in BA vs. healthy hDC, pulsing hDC from BA with OfHz with LPS induced significant increases in expression of IL-10 and IL-12?, although not of TNF-? or tumor growth factor-beta (TGF-?). Conclusions: Liver fluke hemozoin OfHz stimulated production of Th1 inducer and anti-inflammatory cytokines IL-10 and IL-12? from BA-hDC pulsed with OfHz, an outcome that enhances our understanding of the mechanisms whereby opisthorchiasis contributes to protection against the atopic disease in liver fluke infection-endemic regions.

SUBMITTER: Saltykova IV

PROVIDER: S-EPMC6843058 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Hemozoin From the Liver Fluke, Opisthorchis felineus, Modulates Dendritic Cell Responses in Bronchial Asthma Patients.

Saltykova Irina V IV Ittiprasert Wannaporn W Nevskaya Kseniya V KV Dorofeeva Yulia B YB Kirillova Natalia A NA Kulikov Evgeniy S ES Ivanov Vladimir V VV Mann Victoria H VH Pershina Alexandra G AG Brindley Paul J PJ

Frontiers in veterinary science 20191016

Aims: There is a general, inverse relationship between helminth infection and allergic diseases including bronchial asthma (BA). Proteins and other mediators released from parasitic worms exert cogent downmodulation of atopic and other allergic reactivity. We investigated the immune activities of an immortalized murine dendritic cell (mDC) line (JAWSII) and of primary human dendritic cells (hDCs) collected from study participants with and without BA after Opisthorchis felineus hemo ...[more]

PMID: 31750318

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Project description:BackgroundCholangiocarcinoma (CCA)--cancer of the bile ducts--is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome.ResultsApproximately 5,000 randomly selected cDNAs from the adult stage of O. viverrini were characterized and accounted for 1,932 contigs, representing ~14% of the entire transcriptome, and, presently, the largest sequence dataset for any species of liver fluke. Twenty percent of contigs were assigned GO classifications. Abundantly represented protein families included those involved in physiological functions that are essential to parasitism, such as anaerobic respiration, reproduction, detoxification, surface maintenance and feeding. GO assignments were well conserved in relation to other parasitic flukes, however, some categories were over-represented in O. viverrini, such as structural and motor proteins. An assessment of evolutionary relationships showed that O. viverrini was more similar to other parasitic (Clonorchis sinensis and Schistosoma japonicum) than to free-living (Schmidtea mediterranea) flatworms, and 105 sequences had close homologues in both parasitic species but not in S. mediterranea. A total of 164 O. viverrini contigs contained ORFs with signal sequences, many of which were platyhelminth-specific. Examples of convergent evolution between host and parasite secreted/membrane proteins were identified as were homologues of vaccine antigens from other helminths. Finally, ORFs representing secreted proteins with known roles in tumorigenesis were identified, and these might play roles in the pathogenesis of O. viverrini-induced CCA.ConclusionThis gene discovery effort for O. viverrini should expedite molecular studies of cholangiocarcinogenesis and accelerate research focused on developing new interventions, drugs and vaccines, to control O. viverrini and related flukes.

Dataset Information

Hemozoin From the Liver Fluke, Opisthorchis felineus, Modulates Dendritic Cell Responses in Bronchial Asthma Patients.

Publications

Hemozoin From the Liver Fluke, <i>Opisthorchis felineus</i>, Modulates Dendritic Cell Responses in Bronchial Asthma Patients.

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