Single-cell characterization of the human immune landscape reveals dysfunction in monocyte-mediated cellular interactions in symptomatic malaria
- 1Aix Marseille Univ, INSERM, TAGC, Marseille, France.
Abstract
Plasmodium falciparum infection results in a wide range of phenotypes including chronic asymptomatic and symptomatic individuals. The malaria outcome depends, at least in part, on host immune responses mediated by specific cell subsets. Here, we investigated the immune landscape of chronic asymptomatic and symptomatic children using single-cell RNA sequencing. Unexpectedly, we uncovered biologically relevant immune cell complexes, which were further confirmed by imaging flow cytometry. Symptomatic infection was associated with a decrease of cell-cell interactions, particularly between non-classical monocytes and T cells. Non-classical monocytes from symptomatic children exhibited profiles with increased inflammation characterized by enhanced S100A8-S100A9 expression together with decreased expression of interaction-associated genes such as CD86 or ITGAL. Moreover, we demonstrated that inflammatory and cell interaction programs could not be activated simultaneously within the same cell. In addition, the concomitant expression of inflammatory genes and members of the LILR gene family was predominantly observed in monocytes from symptomatic individuals. These findings raise the possibility that enhanced S100A8/S100A9-LILRB1 signaling may contribute to the altered functional state of monocytes in symptomatic malaria and, potentially, may impair their interactions with T cells. Together, our results suggest that immune cell complexes may therefore reveal an additional layer of immune regulation associated with the development of clinical malaria.
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BibTeX
@misc{quatreville2026singlecell,
title = {{Single-cell characterization of the human immune landscape reveals dysfunction in monocyte-mediated cellular interactions in symptomatic malaria}},
author = {L. Quatreville and M. Adjemout and C. Gard and M. Torres and C. Cohen and B. Tumamo Fotso and S. Menard and A. Yaya-Oye Akibou and V. Duplan-Eche and A.-L. Iscache and M. Biarnes-Pelicot and B. Fogang and A. Berry and N. Blanchard and L. Spinelli and S. Nsango and A. Claessens and S. Marquet},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.14.759097},
url = {https://www.biorxiv.org/content/10.64898/2026.10.14.759097v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Single-cell characterization of the human immune landscape reveals dysfunction in monocyte-mediated cellular interactions in symptomatic malaria
AU - L. Quatreville
AU - M. Adjemout
AU - C. Gard
AU - M. Torres
AU - C. Cohen
AU - B. Tumamo Fotso
AU - S. Menard
AU - A. Yaya-Oye Akibou
AU - V. Duplan-Eche
AU - A.-L. Iscache
AU - M. Biarnes-Pelicot
AU - B. Fogang
AU - A. Berry
AU - N. Blanchard
AU - L. Spinelli
AU - S. Nsango
AU - A. Claessens
AU - S. Marquet
PY - 2026
DA - 2026/10/14
PB - bioRxiv
DO - 10.64898/2026.10.14.759097
UR - https://www.biorxiv.org/content/10.64898/2026.10.14.759097v1
AB - Plasmodium falciparum infection results in a wide range of phenotypes including chronic asymptomatic and symptomatic individuals. The malaria outcome depends, at least in part, on host immune responses mediated by specific cell subsets. Here, we investigated the immune landscape of chronic asymptomatic and symptomatic children using single-cell RNA sequencing. Unexpectedly, we uncovered biologically relevant immune cell complexes, which were further confirmed by imaging flow cytometry. Symptomatic infection was associated with a decrease of cell-cell interactions, particularly between non-classical monocytes and T cells. Non-classical monocytes from symptomatic children exhibited profiles with increased inflammation characterized by enhanced S100A8-S100A9 expression together with decreased expression of interaction-associated genes such as CD86 or ITGAL. Moreover, we demonstrated that inflammatory and cell interaction programs could not be activated simultaneously within the same cell. In addition, the concomitant expression of inflammatory genes and members of the LILR gene family was predominantly observed in monocytes from symptomatic individuals. These findings raise the possibility that enhanced S100A8/S100A9-LILRB1 signaling may contribute to the altered functional state of monocytes in symptomatic malaria and, potentially, may impair their interactions with T cells. Together, our results suggest that immune cell complexes may therefore reveal an additional layer of immune regulation associated with the development of clinical malaria.
ER -