Cargando…
Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin
Plasmodium falciparum malaria is the most severe form of malaria with several complications. The malaria pigment‐hemozoin (Hz) is associated with severe anemia, cytokine dysfunction, and immunosuppression, thus making it an interesting target for developing new strategies for antimalarial therapy. M...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436431/ https://www.ncbi.nlm.nih.gov/pubmed/29877619 http://dx.doi.org/10.1002/mbo3.651 |
_version_ | 1783406813269458944 |
---|---|
author | Bobade, Deepali Khandare, Ashwin V. Deval, Mangesh Shastry, Padma Deshpande, Prakash |
author_facet | Bobade, Deepali Khandare, Ashwin V. Deval, Mangesh Shastry, Padma Deshpande, Prakash |
author_sort | Bobade, Deepali |
collection | PubMed |
description | Plasmodium falciparum malaria is the most severe form of malaria with several complications. The malaria pigment‐hemozoin (Hz) is associated with severe anemia, cytokine dysfunction, and immunosuppression, thus making it an interesting target for developing new strategies for antimalarial therapy. Monocytes (MO) in circulation actively ingest Hz released by Plasmodium parasites and secrete pro‐ and anti‐inflammatory cytokines. M1 and M2 types represent the two major forms of MO/macrophages (MQ) with distinct phenotypes and opposing functions. Imbalance in the polarization of these types is reported in many infectious diseases. Though the association of Hz with immunosuppression is well documented, its role in activation of MO in context of M1/M2 phenotypes remains to be addressed. We report here that natural Hz drives human MO toward M2‐like phenotype as evidenced by the expression of M2 signature markers. Hz‐fed MO showed elevated transcript and secreted level of IL‐10, CCL17, CCL1, expression of mannose‐binding lectin receptor (CD206), and arginase activity. Hz attenuated HLA‐DR expression, nitric oxide, and reactive oxygen species production, which are the features of M1 phenotype. Our data also implicate the involvement of p38 MAPK, PI3K/AKT, and NF‐κB signaling pathways in skewing of Hz‐fed MO toward M2‐like type and suppression of mitogen‐stimulated lymphocyte proliferation. Importantly, antimalarial drugs—chloroquine and artemisinin—partially reversed activation of Hz‐induced MO toward M2‐like phenotype. Considering the limitations in the current therapeutic options for malaria, we propose that these drugs may be re‐examined for their potential as immunomodulators and candidates for adjunctive treatment in malaria. |
format | Online Article Text |
id | pubmed-6436431 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64364312019-04-08 Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin Bobade, Deepali Khandare, Ashwin V. Deval, Mangesh Shastry, Padma Deshpande, Prakash Microbiologyopen Original Articles Plasmodium falciparum malaria is the most severe form of malaria with several complications. The malaria pigment‐hemozoin (Hz) is associated with severe anemia, cytokine dysfunction, and immunosuppression, thus making it an interesting target for developing new strategies for antimalarial therapy. Monocytes (MO) in circulation actively ingest Hz released by Plasmodium parasites and secrete pro‐ and anti‐inflammatory cytokines. M1 and M2 types represent the two major forms of MO/macrophages (MQ) with distinct phenotypes and opposing functions. Imbalance in the polarization of these types is reported in many infectious diseases. Though the association of Hz with immunosuppression is well documented, its role in activation of MO in context of M1/M2 phenotypes remains to be addressed. We report here that natural Hz drives human MO toward M2‐like phenotype as evidenced by the expression of M2 signature markers. Hz‐fed MO showed elevated transcript and secreted level of IL‐10, CCL17, CCL1, expression of mannose‐binding lectin receptor (CD206), and arginase activity. Hz attenuated HLA‐DR expression, nitric oxide, and reactive oxygen species production, which are the features of M1 phenotype. Our data also implicate the involvement of p38 MAPK, PI3K/AKT, and NF‐κB signaling pathways in skewing of Hz‐fed MO toward M2‐like type and suppression of mitogen‐stimulated lymphocyte proliferation. Importantly, antimalarial drugs—chloroquine and artemisinin—partially reversed activation of Hz‐induced MO toward M2‐like phenotype. Considering the limitations in the current therapeutic options for malaria, we propose that these drugs may be re‐examined for their potential as immunomodulators and candidates for adjunctive treatment in malaria. John Wiley and Sons Inc. 2018-06-07 /pmc/articles/PMC6436431/ /pubmed/29877619 http://dx.doi.org/10.1002/mbo3.651 Text en © 2018 National Centre for Cell Sciences. MicrobiologyOpen published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Bobade, Deepali Khandare, Ashwin V. Deval, Mangesh Shastry, Padma Deshpande, Prakash Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin |
title | Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin |
title_full | Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin |
title_fullStr | Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin |
title_full_unstemmed | Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin |
title_short | Hemozoin‐induced activation of human monocytes toward M2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin |
title_sort | hemozoin‐induced activation of human monocytes toward m2‐like phenotype is partially reversed by antimalarial drugs—chloroquine and artemisinin |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436431/ https://www.ncbi.nlm.nih.gov/pubmed/29877619 http://dx.doi.org/10.1002/mbo3.651 |
work_keys_str_mv | AT bobadedeepali hemozoininducedactivationofhumanmonocytestowardm2likephenotypeispartiallyreversedbyantimalarialdrugschloroquineandartemisinin AT khandareashwinv hemozoininducedactivationofhumanmonocytestowardm2likephenotypeispartiallyreversedbyantimalarialdrugschloroquineandartemisinin AT devalmangesh hemozoininducedactivationofhumanmonocytestowardm2likephenotypeispartiallyreversedbyantimalarialdrugschloroquineandartemisinin AT shastrypadma hemozoininducedactivationofhumanmonocytestowardm2likephenotypeispartiallyreversedbyantimalarialdrugschloroquineandartemisinin AT deshpandeprakash hemozoininducedactivationofhumanmonocytestowardm2likephenotypeispartiallyreversedbyantimalarialdrugschloroquineandartemisinin |