Investigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica
Abstract Background Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by the protozoan parasite Leishmania. In Ethiopia, CL is mainly caused by Leishmania aethiopica and can present in different clinical forms. The aim of this study was to assess whether these different forms...
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BMC
2024-10-01
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| Series: | Infectious Diseases of Poverty |
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| Online Access: | https://doi.org/10.1186/s40249-024-01244-x |
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| author | Endalew Yizengaw Yegnasew Takele Susanne Franssen Bizuayehu Gashaw Mulat Yimer Emebet Adem Endalkachew Nibret Gizachew Yismaw Edward Cruz Cervera Kefale Ejigu Dessalegn Tamiru Abaineh Munshea Ingrid Müller Richard Weller James A. Cotton Pascale Kropf |
| author_facet | Endalew Yizengaw Yegnasew Takele Susanne Franssen Bizuayehu Gashaw Mulat Yimer Emebet Adem Endalkachew Nibret Gizachew Yismaw Edward Cruz Cervera Kefale Ejigu Dessalegn Tamiru Abaineh Munshea Ingrid Müller Richard Weller James A. Cotton Pascale Kropf |
| author_sort | Endalew Yizengaw |
| collection | DOAJ |
| description | Abstract Background Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by the protozoan parasite Leishmania. In Ethiopia, CL is mainly caused by Leishmania aethiopica and can present in different clinical forms. The aim of this study was to assess whether these different forms are associated with differences in parasite genetic and host systemic immune signatures. Methods Here we analysed the whole genome sequence data for 48 clinical parasite isolates and the systemic immune signature from a cohort of CL patients, who were recruited in Nefas Mewcha, Northern Ethiopia, from January 2019 to January 2022. Results Our results show that parasites from CL cases with different presentations in a single Ethiopian setting are from the same genetic population based on a permutation test of genome-wide similarity. Furthermore, a logistic regression test for genome wide association did not identify any individual genetic variants significantly associated with disease presentation. We also measured plasma chemokine and cytokine levels of 129 CL patients presenting with different forms of CL. None of the chemokine [eotaxin, eotaxin-3, interleukin (IL)-8, interferon (IFN)-γ-induced protein-10 (IP-10), monocyte chemoattractant protein (MCP)-1, MCP-4, macrophage-derived chemokines (MDC), macrophage inflammatory protein (MIP)-1α, MIP-1β and thymus- and activation-regulated chemokine (TARC)] or cytokine (IFN-γ, IL-1β, interleukin-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis factor-α) levels measured were significantly different between the different clinical presentations of CL, as measured by Kruskal–Wallis test. We also compared those with healthy nonendemic controls: our results show a chemokine (IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β and TARC) but not a cytokine immune signature in patients with CL as compared to healthy nonendemic controls, as measured by Mann-Whitney test. Conclusions The results of our study did not identify a systemic immune signature or parasite genetic factors associated with different clinical presentation of CL. Graphical abstract |
| format | Article |
| id | doaj-art-daea6f13c3c14fdb98647cad083e5421 |
| institution | OA Journals |
| issn | 2049-9957 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
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| series | Infectious Diseases of Poverty |
| spelling | doaj-art-daea6f13c3c14fdb98647cad083e54212025-08-20T02:17:46ZengBMCInfectious Diseases of Poverty2049-99572024-10-0113111410.1186/s40249-024-01244-xInvestigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopicaEndalew Yizengaw0Yegnasew Takele1Susanne Franssen2Bizuayehu Gashaw3Mulat Yimer4Emebet Adem5Endalkachew Nibret6Gizachew Yismaw7Edward Cruz Cervera8Kefale Ejigu9Dessalegn Tamiru10Abaineh Munshea11Ingrid Müller12Richard Weller13James A. Cotton14Pascale Kropf15Department of Medical Laboratory Science, College of Medicine and Health Sciences, Bahir Dar UniversityDepartment of Infectious Disease, Imperial College LondonWellcome Sanger Institute, Wellcome Genome CampusAmhara Public Health InstituteDepartment of Medical Laboratory Science, College of Medicine and Health Sciences, Bahir Dar UniversityUniversity of Greenwich at MedwayInstitute of Biotechnology, Bahir Dar UniversityAmhara Public Health InstituteDepartment of Infectious Disease, Imperial College LondonAmhara Public Health InstituteNefas Mewcha HospitalInstitute of Biotechnology, Bahir Dar UniversityDepartment of Infectious Disease, Imperial College LondonDepartment of Dermatology, University of EdinburghWellcome Sanger Institute, Wellcome Genome CampusDepartment of Infectious Disease, Imperial College LondonAbstract Background Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by the protozoan parasite Leishmania. In Ethiopia, CL is mainly caused by Leishmania aethiopica and can present in different clinical forms. The aim of this study was to assess whether these different forms are associated with differences in parasite genetic and host systemic immune signatures. Methods Here we analysed the whole genome sequence data for 48 clinical parasite isolates and the systemic immune signature from a cohort of CL patients, who were recruited in Nefas Mewcha, Northern Ethiopia, from January 2019 to January 2022. Results Our results show that parasites from CL cases with different presentations in a single Ethiopian setting are from the same genetic population based on a permutation test of genome-wide similarity. Furthermore, a logistic regression test for genome wide association did not identify any individual genetic variants significantly associated with disease presentation. We also measured plasma chemokine and cytokine levels of 129 CL patients presenting with different forms of CL. None of the chemokine [eotaxin, eotaxin-3, interleukin (IL)-8, interferon (IFN)-γ-induced protein-10 (IP-10), monocyte chemoattractant protein (MCP)-1, MCP-4, macrophage-derived chemokines (MDC), macrophage inflammatory protein (MIP)-1α, MIP-1β and thymus- and activation-regulated chemokine (TARC)] or cytokine (IFN-γ, IL-1β, interleukin-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis factor-α) levels measured were significantly different between the different clinical presentations of CL, as measured by Kruskal–Wallis test. We also compared those with healthy nonendemic controls: our results show a chemokine (IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β and TARC) but not a cytokine immune signature in patients with CL as compared to healthy nonendemic controls, as measured by Mann-Whitney test. Conclusions The results of our study did not identify a systemic immune signature or parasite genetic factors associated with different clinical presentation of CL. Graphical abstracthttps://doi.org/10.1186/s40249-024-01244-xCutaneous leishmaniasisLeishmania aethiopicaGeneticsCytokinesChemokinesPlasma |
| spellingShingle | Endalew Yizengaw Yegnasew Takele Susanne Franssen Bizuayehu Gashaw Mulat Yimer Emebet Adem Endalkachew Nibret Gizachew Yismaw Edward Cruz Cervera Kefale Ejigu Dessalegn Tamiru Abaineh Munshea Ingrid Müller Richard Weller James A. Cotton Pascale Kropf Investigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica Infectious Diseases of Poverty Cutaneous leishmaniasis Leishmania aethiopica Genetics Cytokines Chemokines Plasma |
| title | Investigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica |
| title_full | Investigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica |
| title_fullStr | Investigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica |
| title_full_unstemmed | Investigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica |
| title_short | Investigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica |
| title_sort | investigation of parasite genetic variation and systemic immune responses in patients presenting with different clinical presentations of cutaneous leishmaniasis caused by leishmania aethiopica |
| topic | Cutaneous leishmaniasis Leishmania aethiopica Genetics Cytokines Chemokines Plasma |
| url | https://doi.org/10.1186/s40249-024-01244-x |
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