Müller, I. | Search bioRxiv

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↗

bioRxiv2018

Sex differences in fear regulation and reward seeking behaviors in a fear-safety-reward discrimination task

Reward availability and the potential for danger or safety potently regulates emotion. Despite women being more likely than men to develop emotion dysregulation disorders, there are comparatively few studies investigating fear, safety and reward regulation in females. Here, we show that female Long Evans rats do not suppress conditioned freezing in the presence of a safety cue, nor do they extinguish their freezing response, whereas males do both. Females were also more reward responsive during the reward cue until the first footshock exposure, at which point there were no sex differences in reward seeking to the reward cue. Darting analyses indicate females might be able to regulate this behavior in response to the safety cue, suggesting they might be able to discriminate between fear and safety cues but do not demonstrate this with conditioned suppression of the freezing behavior. However, levels of darting in this study were too low to make any clear conclusions. In summary, females showed a significantly different behavioral profile than males in a task that tests the ability to discriminate among fear, safety and reward cues. This paradigm offers a great opportunity to test for mechanisms that are generating these behavioral sex differences in learned safety and reward seeking.

neuroscience↗