The circulating plasma microRNA signature in human visceral leishmaniasis
ABSTRACT Visceral leishmaniasis (VL) is a vector-borne disease caused by the obligate intracellular protozoan Leishmania donovani in India. VL can be complicated by post-kala-azar dermal leishmaniasis (PKDL), a macular or nodular rash that develops in 10%–20% of patients after treatment of VL in Ind...
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American Society for Microbiology
2025-02-01
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| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00646-24 |
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| author | Ritirupa Roy Cinthia L. Hudachek Shashi Bhushan Chauhan Shashi Kumar Awnish Kumar Bayan Zhanbolat Madhukar Rai Rajiv Kumar Shyam Sundar Mary E. Wilson |
| author_facet | Ritirupa Roy Cinthia L. Hudachek Shashi Bhushan Chauhan Shashi Kumar Awnish Kumar Bayan Zhanbolat Madhukar Rai Rajiv Kumar Shyam Sundar Mary E. Wilson |
| author_sort | Ritirupa Roy |
| collection | DOAJ |
| description | ABSTRACT Visceral leishmaniasis (VL) is a vector-borne disease caused by the obligate intracellular protozoan Leishmania donovani in India. VL can be complicated by post-kala-azar dermal leishmaniasis (PKDL), a macular or nodular rash that develops in 10%–20% of patients after treatment of VL in India. Patients with PKDL are infectious to sand flies, promoting further transmission of the parasite. MicroRNAs (miRNAs) are 18–25 nt, non-coding RNAs that simultaneously regulate the expression of several or many target transcripts. This study was based on the hypothesis that the host response to L. donovani is modified by distinct sets of miRNAs in VL or PKDL and that these might differ from healthy controls. We investigated this hypothesis using a NanoString panel to profile the miRNAs expressed in the plasma of patients with VL or PKDL diagnosed at a hospital in Bihar, India. We compared these to plasma microRNAs of healthy control individuals from the same endemic villages. miRNAs hsa-miR-223-3p, hsa-miR-191-5p, hsa-miR-23a-3p, and hsa-1285-5p were significantly higher in the plasma samples from patients with VL compared to either PKDL or endemic controls. Prediction programs highlighted potential mRNA targeted by these miRNAs, among which we verified the down-modulation of several transcripts belonging to the NFκB and NLRP3 inflammasome pathways in circulating leukocytes of VL patients. By contrast, miRNA patterns in subjects with PKDL were similar to control subjects, possibly suggesting that the pathogenic immune response during PKDL is primarily localized in the skin.IMPORTANCEInfection of humans with the protozoan Leishmania donovani can be asymptomatic or it can cause fatal visceral leishmaniasis (VL), sometimes followed by the cutaneous complication PKDL. Parasites are spread through sand fly bites in endemic regions, and parasites in post-kala-azar dermal leishmaniasis (PKDL) skin lesions are a source of prolonged parasite transmission to sand flies, compromising disease eradication efforts. Since microRNAs can simultaneously modify the expression of multiple genes, we examined microRNAs in the blood that might be partial determinants of pathogenic responses leading to VL or PKDL. Our studies revealed several miRNAs expressed that are elevated in the plasma of patients with VL, which suppress some of the inflammatory responses that promote parasite killing. However, miRNA profiles were very similar between PKDL patients and controls, raising the possibility that major factors that lead to prolonged retention of parasites in the skin during PKDL are not systemic but are localized in the skin. |
| format | Article |
| id | doaj-art-5ed5abc83f224e63a43904bfb3f4f673 |
| institution | DOAJ |
| issn | 2379-5042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | American Society for Microbiology |
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| spelling | doaj-art-5ed5abc83f224e63a43904bfb3f4f6732025-08-20T03:16:21ZengAmerican Society for MicrobiologymSphere2379-50422025-02-0110210.1128/msphere.00646-24The circulating plasma microRNA signature in human visceral leishmaniasisRitirupa Roy0Cinthia L. Hudachek1Shashi Bhushan Chauhan2Shashi Kumar3Awnish Kumar4Bayan Zhanbolat5Madhukar Rai6Rajiv Kumar7Shyam Sundar8Mary E. Wilson9Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USADepartment of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USACentre of Experimental Medicine & Surgery, Banaras Hindu University, Varanasi, Uttar Pradesh, IndiaDepartment of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, IndiaCentre of Experimental Medicine & Surgery, Banaras Hindu University, Varanasi, Uttar Pradesh, IndiaVeterans’ Affairs Medical Center, Iowa City, Iowa, USADepartment of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, IndiaCentre of Experimental Medicine & Surgery, Banaras Hindu University, Varanasi, Uttar Pradesh, IndiaDepartment of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, IndiaDepartment of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USAABSTRACT Visceral leishmaniasis (VL) is a vector-borne disease caused by the obligate intracellular protozoan Leishmania donovani in India. VL can be complicated by post-kala-azar dermal leishmaniasis (PKDL), a macular or nodular rash that develops in 10%–20% of patients after treatment of VL in India. Patients with PKDL are infectious to sand flies, promoting further transmission of the parasite. MicroRNAs (miRNAs) are 18–25 nt, non-coding RNAs that simultaneously regulate the expression of several or many target transcripts. This study was based on the hypothesis that the host response to L. donovani is modified by distinct sets of miRNAs in VL or PKDL and that these might differ from healthy controls. We investigated this hypothesis using a NanoString panel to profile the miRNAs expressed in the plasma of patients with VL or PKDL diagnosed at a hospital in Bihar, India. We compared these to plasma microRNAs of healthy control individuals from the same endemic villages. miRNAs hsa-miR-223-3p, hsa-miR-191-5p, hsa-miR-23a-3p, and hsa-1285-5p were significantly higher in the plasma samples from patients with VL compared to either PKDL or endemic controls. Prediction programs highlighted potential mRNA targeted by these miRNAs, among which we verified the down-modulation of several transcripts belonging to the NFκB and NLRP3 inflammasome pathways in circulating leukocytes of VL patients. By contrast, miRNA patterns in subjects with PKDL were similar to control subjects, possibly suggesting that the pathogenic immune response during PKDL is primarily localized in the skin.IMPORTANCEInfection of humans with the protozoan Leishmania donovani can be asymptomatic or it can cause fatal visceral leishmaniasis (VL), sometimes followed by the cutaneous complication PKDL. Parasites are spread through sand fly bites in endemic regions, and parasites in post-kala-azar dermal leishmaniasis (PKDL) skin lesions are a source of prolonged parasite transmission to sand flies, compromising disease eradication efforts. Since microRNAs can simultaneously modify the expression of multiple genes, we examined microRNAs in the blood that might be partial determinants of pathogenic responses leading to VL or PKDL. Our studies revealed several miRNAs expressed that are elevated in the plasma of patients with VL, which suppress some of the inflammatory responses that promote parasite killing. However, miRNA profiles were very similar between PKDL patients and controls, raising the possibility that major factors that lead to prolonged retention of parasites in the skin during PKDL are not systemic but are localized in the skin.https://journals.asm.org/doi/10.1128/msphere.00646-24visceral leishmaniasispost-kala-azar dermal leishmaniasismicroRNAgene expressionIndia |
| spellingShingle | Ritirupa Roy Cinthia L. Hudachek Shashi Bhushan Chauhan Shashi Kumar Awnish Kumar Bayan Zhanbolat Madhukar Rai Rajiv Kumar Shyam Sundar Mary E. Wilson The circulating plasma microRNA signature in human visceral leishmaniasis mSphere visceral leishmaniasis post-kala-azar dermal leishmaniasis microRNA gene expression India |
| title | The circulating plasma microRNA signature in human visceral leishmaniasis |
| title_full | The circulating plasma microRNA signature in human visceral leishmaniasis |
| title_fullStr | The circulating plasma microRNA signature in human visceral leishmaniasis |
| title_full_unstemmed | The circulating plasma microRNA signature in human visceral leishmaniasis |
| title_short | The circulating plasma microRNA signature in human visceral leishmaniasis |
| title_sort | circulating plasma microrna signature in human visceral leishmaniasis |
| topic | visceral leishmaniasis post-kala-azar dermal leishmaniasis microRNA gene expression India |
| url | https://journals.asm.org/doi/10.1128/msphere.00646-24 |
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