Biology subjects

Cruz Cervera, E.

Publications and source records attributed to Cruz Cervera, E..

3 recordsLinked to original sources

bioRxiv2025

Different isolates of Leishmania aethiopica elicit distinct effector functions in primary human monocytes

In Ethiopia, cutaneous leishmaniasis (CL) is caused by Leishmania (L.) aethiopica and presents as a spectrum of clinical forms ranging from self-healing to persistent, disfiguring lesions. Monocytes are some of the first cells to encounter Leishmania parasites in the host. Despite this, their role in L. aethiopica infection has not been investigated. In this study, primary human monocytes were co-incubated with different L. aethiopica isolates - three isolates recently collected from CL patients and one long-term cultured isolate - and their main effector functions were evaluated. After 2 hours of co-incubation, over 30% of monocytes associated with all four L. aethiopica isolates, with significantly higher association with recently isolated L. aethiopica than with the long-term cultured parasites. Phagocytosis of L. aethiopica parasites by monocytes was confirmed by confocal microscopy. Co-incubation of monocytes with all L. aethiopica isolates resulted in upregulation of reactive oxygen species in monocytes. Following incubation of monocytes with all L. aethiopica, five chemokines - monocyte chemoattractant protein (MCP)-1, MCP-4, macrophage inflammatory protein (MIP)-1, MIP-1{beta}, and interleukin (IL-8) - and four cytokines - tumour necrosis factor (TNF)-, IL-1{beta}, IL-6, and IL-10 - were detected. Our results show that the interaction of monocytes with the long-term cultured L. aethiopica differ as compared to those recently collected from CL patients. Furthermore, we define an in vitro model for the investigation of monocyte effector functions that may be useful to elucidate the role that parasites and their interactions with monocytes play in the different presentations of lesions caused by L. aethiopica.

immunology↗

bioRxiv2024

Distinct neutrophil effector functions in response to different isolates of Leishmania aethiopica

BackgroundIn Ethiopia, cutaneous leishmaniasis is mainly caused by Leishmania (L.) aethiopica parasites and presents in three main clinical forms. It is still not clear if the host immune response plays a role in the development of these different presentations. Since neutrophils are likely to be one of the first immune cells present at the site of the sand fly bite, we set up an in vitro model of infection of neutrophils with L. aethiopica and assessed neutrophil effector functions. We used freshly isolated clinical isolates and one isolate that has been kept in culture for decades. ResultsOur results showed by flow cytometry that up to a quarter of neutrophils were associated with L. aethiopica; and confocal microscopy demonstrated that all isolates can be internalised. The clinical isolates of L. aethiopica associated more efficiently with neutrophils than the long-term cultured L. aethiopica. At 18hrs, two distinct populations of neutrophils were identified that associated with L. aethiopica, CD15high and CD15low neutrophils. Our results also showed that all parasites induced apoptosis in L. aethiopica-associated neutrophils. Moreover, our results showed that after 2 hrs, L. aethiopica-associated neutrophils upregulated their production of ROS, but to a greater extent with the long-term cultured L. aethiopica. After 18 hrs of incubation, CD15lowparasite+ showed an impaired ability to produce ROS as compared to CD15highparasite+. ConclusionUsing this in vitro model, our results show that different L. aethiopica parasite isolates, most notably long-term cultured parasites, impacted differently on neutrophil effector functions.

immunology↗

bioRxiv2024

Parasite genetic variation and systemic immune responses are not associated with different clinical presentations of cutaneous leishmaniasis caused by Leishmania aethiopica

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease, caused by the protozoan parasite Leishmania (L.). It is endemic to 90 countries and causes >200,000 new infections each year. In Ethiopia, CL is mainly caused by L. aethiopica and can present in different clinical forms: localised cutaneous leishmaniasis (LCL); mucocutaneous leishmaniasis (MCL), where the mucosa of the nose and/or the mouth are affected; and diffuse CL (DCL), characterised by non-ulcerating nodules. Persistent forms of LCL, as well as MCL and DCL, require treatment but are difficult to treat successfully and can lead to permanent disfigurement, social stigmatisation, and a mental health burden. The mechanisms behind the development of these different presentations of CL are not clearly understood, and both parasite and host factors could be involved. Here we analysed the whole genome sequence data for 48 clinical parasite isolates and show that parasites from CL cases with different presentations in a single Ethiopian setting are from the same genetic population. Furthermore, we 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 cytokine or chemokine levels measured were significantly different between the different clinical presentations of CL. We also compared those with healthy nonendemic controls: our results show a chemokine but not a cytokine immune signature in patients with CL as compared to healthy nonendemic controls.

genomics↗