Modulation of the immune response and infection pattern to Leishmania donovani in visceral leishmaniasis due to arsenic exposure: An in vitro study.
The arsenic contamination of ground water in visceral leishmaniasis (VL) endemic areas in Bihar, India leads to human exposure through drinking water. Possibly, the consumed arsenic (As) accumulates in the tissues of VL patients, who subsequently internalize intracellular amastigotes to confer resis...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0210737 |
| _version_ | 1831761870398160896 |
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| author | Ghufran Ahmed Ajit K Thakur Pushpanjali Snehil Sanjay K Chaturvedi Pushkar Shivam Fauzia Jamal Manish K Singh Sanjiva Bimal Subhankar K Singh Sunil K Choudhary Pradeep Das Shyam Narayan |
| author_facet | Ghufran Ahmed Ajit K Thakur Pushpanjali Snehil Sanjay K Chaturvedi Pushkar Shivam Fauzia Jamal Manish K Singh Sanjiva Bimal Subhankar K Singh Sunil K Choudhary Pradeep Das Shyam Narayan |
| author_sort | Ghufran Ahmed |
| collection | DOAJ |
| description | The arsenic contamination of ground water in visceral leishmaniasis (VL) endemic areas in Bihar, India leads to human exposure through drinking water. Possibly, the consumed arsenic (As) accumulates in the tissues of VL patients, who subsequently internalize intracellular amastigotes to confer resistance against chemotherapy to the parasite, leading to modulation in the host's immune response. This hypothesis appears to be consistent with the in vitro findings that in arsenic-exposed parasites, the mitochondrial membrane potential became depolarized, whereas the reduced thiol and lactate production was overexpressed with enhanced glucose consumption; therefore, the reduced thiol possibly supports an immunosuppressive state in the host cells. This observation was well supported by the down-regulated expression of pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α) with a suppressed anti-leishmanial function of macrophage (NO, ROS). In contrast, the pathophysiological mechanism of VL has received ample support by the promotion of Th2 cytokines (IL-4 and IL-10) in the presence of arsenic-exposed Leishmania parasites (LdAS). Dysfunction of mitochondria and the overexpression of lactate production raise the possibility of the Warburg effect being operative through the up-regulation of glucose consumption by parasites to enhance the energy production, possibly augmenting virulence. Therefore, we surmise from our data that arsenic exposure to Leishmania donovani modulates the immune response and infection pattern by impairing parasite function, which may affect the anti-leishmanial effect in VL. |
| first_indexed | 2024-12-22T04:56:19Z |
| format | Article |
| id | doaj.art-bd975bc1cc1444d8b1e064f9ba7ffc91 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T04:56:19Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bd975bc1cc1444d8b1e064f9ba7ffc912022-12-21T18:38:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01142e021073710.1371/journal.pone.0210737Modulation of the immune response and infection pattern to Leishmania donovani in visceral leishmaniasis due to arsenic exposure: An in vitro study.Ghufran AhmedAjit K ThakurPushpanjaliSnehilSanjay K ChaturvediPushkar ShivamFauzia JamalManish K SinghSanjiva BimalSubhankar K SinghSunil K ChoudharyPradeep DasShyam NarayanThe arsenic contamination of ground water in visceral leishmaniasis (VL) endemic areas in Bihar, India leads to human exposure through drinking water. Possibly, the consumed arsenic (As) accumulates in the tissues of VL patients, who subsequently internalize intracellular amastigotes to confer resistance against chemotherapy to the parasite, leading to modulation in the host's immune response. This hypothesis appears to be consistent with the in vitro findings that in arsenic-exposed parasites, the mitochondrial membrane potential became depolarized, whereas the reduced thiol and lactate production was overexpressed with enhanced glucose consumption; therefore, the reduced thiol possibly supports an immunosuppressive state in the host cells. This observation was well supported by the down-regulated expression of pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α) with a suppressed anti-leishmanial function of macrophage (NO, ROS). In contrast, the pathophysiological mechanism of VL has received ample support by the promotion of Th2 cytokines (IL-4 and IL-10) in the presence of arsenic-exposed Leishmania parasites (LdAS). Dysfunction of mitochondria and the overexpression of lactate production raise the possibility of the Warburg effect being operative through the up-regulation of glucose consumption by parasites to enhance the energy production, possibly augmenting virulence. Therefore, we surmise from our data that arsenic exposure to Leishmania donovani modulates the immune response and infection pattern by impairing parasite function, which may affect the anti-leishmanial effect in VL.https://doi.org/10.1371/journal.pone.0210737 |
| spellingShingle | Ghufran Ahmed Ajit K Thakur Pushpanjali Snehil Sanjay K Chaturvedi Pushkar Shivam Fauzia Jamal Manish K Singh Sanjiva Bimal Subhankar K Singh Sunil K Choudhary Pradeep Das Shyam Narayan Modulation of the immune response and infection pattern to Leishmania donovani in visceral leishmaniasis due to arsenic exposure: An in vitro study. PLoS ONE |
| title | Modulation of the immune response and infection pattern to Leishmania donovani in visceral leishmaniasis due to arsenic exposure: An in vitro study. |
| title_full | Modulation of the immune response and infection pattern to Leishmania donovani in visceral leishmaniasis due to arsenic exposure: An in vitro study. |
| title_fullStr | Modulation of the immune response and infection pattern to Leishmania donovani in visceral leishmaniasis due to arsenic exposure: An in vitro study. |
| title_full_unstemmed | Modulation of the immune response and infection pattern to Leishmania donovani in visceral leishmaniasis due to arsenic exposure: An in vitro study. |
| title_short | Modulation of the immune response and infection pattern to Leishmania donovani in visceral leishmaniasis due to arsenic exposure: An in vitro study. |
| title_sort | modulation of the immune response and infection pattern to leishmania donovani in visceral leishmaniasis due to arsenic exposure an in vitro study |
| url | https://doi.org/10.1371/journal.pone.0210737 |
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