Advances in the Immunology of the Host-Parasite Interactions in African Trypanosomosis, including Single-Cell Transcriptomics

Abstract

Trypanosomes are single-celled extracellular parasites that infect mammals, including humans and livestock, causing global public health concerns and economic losses. These parasites cycle between insect vectors, such as tsetse flies and vertebrate hosts, undergoing morphological, cellular, and biochemical changes. They have remarkable immune evasion mechanisms to escape the host's innate and adaptive immune responses, such as surface coat antigenic variation and the induction of the loss of specificity and memory of antibody responses, enabling the prolongation of infection. Since trypanosomes circulate through the host body in blood and lymph fluid and invade various organs, understanding the interaction between trypanosomes and tissue niches is essential. Here, we present an up-to-date overview of host-parasite interactions and survival strategies for trypanosomes by introducing and discussing the latest studies investigating the transcriptomics of parasites according to life cycle stages, as well as host cells in various tissues and organs, using single-cell and spatial sequencing applications. In recent years, this information has improved our understanding of trypanosomosis by deciphering the diverse populations of parasites in the developmental process, as well as the highly heterogeneous immune and tissue-resident cells involved in anti-trypanosome responses. Ultimately, the goal of these approaches is to gain an in-depth understanding of parasite biology and host immunity, potentially leading to new vaccination and therapeutic strategies against trypanosomosis.

Keywords: African trypanosomes; immunity; organ; single-cell sequencing; transcriptomics.

Figure 1

Simplified life cycle of T. brucei and particular forms residing in host tissue. Trypanosoma brucei is a parasite that uses the tsetse fly as its definite host, colonizing the midgut and salivary glands. Infection of the mammalian ‘reservoir’ is accomplished by injection of metacyclic parasites that quickly transform into dividing long slender bloodstream forms (BSFs). From here, tissues are invaded, such as the skin and adipose tissue, where transcriptome research has allowed to identify uniquely adapted parasite forms such as skin tissue forms (STFs) and adipose tissue forms (ATFs). Ultimately, the mammalian brain is invaded where the main pathology that characterizes HAT occurs (figure created using BioRender.com).

Figure 2

Overview of trypanosome–host interactions in different organs. Trypanosomes colonize multiple organs of the mammalian hosts and invade tissues through blood and lymphatic vessels. This results in local modulations of host immunity and subsequent pathological outcomes (figure created using BioRender.com).