bioRxiv Science⌕ Search

Biology subjects

Mulaw, T.

Publications and source records attributed to Mulaw, T..

2 recordsLinked to original sources
bioRxiv2024

Altered co-stimulatory and inhibitory receptors on monocyte subsets in patients with visceral leishmaniasis

Visceral leishmaniasis (VL) is a neglected tropical disease caused by parasites from the Leishmania (L.) donovani complex. VL is characterised by uncontrolled parasite replication in spleen, liver and bone marrow, and by an impaired immune response and high systemic levels of inflammation. Monocytes have been poorly characterised in VL patients. The aim of this study was to evaluate the expression levels of markers involved in the regulation of T cell responses on different subsets of monocytes from the blood of VL patients and healthy non-endemic controls (HNEC). Monocytes can broadly be divided into three subsets: classical, intermediate and non-classical monocytes. Our results show that the percentages of all three subsets stay similar at the time of VL diagnosis (ToD) and at the end of anti-leishmanial treatment (EoT). We first looked at co-stimulatory receptors: the expression levels of CD40 were significantly increased on classical and intermediate, but not non-classical monocytes, at ToD as compared to EoT and HNEC. CD80 expression levels were also increased on intermediate monocytes at ToD as compared to EoT and HNEC, and on classical monocytes only as compared to HNEC. The levels of CD86 were similar at EoT and ToD and in HNEC on classical and intermediate monocytes, but significantly higher at EoT on non-classical monocytes. We also looked at an inhibitory molecule, PD-L1. Our results show that the expression levels of PD-L1 is significantly higher on all three monocyte subsets at ToD as compared to HNEC, and to EoT on classical and intermediate monocytes. These results show that monocytes from the blood of VL patients upregulate both co-stimulatory and inhibitory receptors and that their expression levels are restored at EoT.

immunology↗
bioRxiv2021

Immunological factors, but not clinical features, predict visceral leishmaniasis relapse in patients co-infected with HIV

Visceral leishmaniasis (VL) has emerged as a clinically important opportunistic infection in HIV patients, as VL/HIV co-infected patients suffer from frequent VL relapse. Here, we followed cohorts of VL patients with or without HIV co-infections in Ethiopia and collected detailed clinical and immunological data during 12 months of follow-up. By the end of the study 78.1% of VL/HIV patients, but none of the VL only patients, had relapsed. Despite clinically defined cure, VL/HIV patients maintained high parasite loads, low BMI, hepatosplenomegaly and pancytopenia throughout follow-up. During detailed immunological study throughout the follow-up period, we identified three markers associated with VL relapse: i) failure to restore antigen-specific production of IFN{gamma}, ii) persistently low CD4+ T cell counts, and iii) high expression of PD1 on CD4+ T cells. We show that these three markers combine well in predicting VL relapse, and that all three measurements are needed for optimal predictive power. These three immunological markers can be measured in primary hospital settings in Ethiopia and can predict VL relapse after anti-leishmanial therapy. The use of our prediction model has the potential to improve disease management and patient care.

immunology↗